Covered studies library

Follow the publication. Keep the interpretation separate.

Browse 133 unique primary studies and governing syntheses used across all 55 released stories. This is a publication-maintained reading aid—not a complete literature database, evidence ranking or recommendation.

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133 of 133 publication records shown

Evidence synthesis

8 covered publications

peer-reviewed-synthesis · peer-reviewed

Whi Current Synthesis

DOI 10.1001/jama.2024.6542

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-synthesis
Study designEvidence synthesispeer reviewed evidence synthesis
Population or modelPeoplerandomized human chronic-disease evidence plus long-term mortality and regimen-specific breast-cancer follow-up
Population/model
postmenopausal women considered by regimen, age, timing and indication
Intervention and comparator
menopausal hormone therapy; randomized trials
Duration
Not separately structured in this publication record
Measured outcome
clinical-practice interpretation of WHI randomized evidence

What the covered evidence found

WHI tested chronic-disease prevention rather than symptom relief; current synthesis recognizes an individualized symptom-treatment role while not supporting hormone therapy for general chronic-disease or longevity prevention. · Age and time-since-menopause subgroup patterns are secondary context and do not override the overall randomized comparisons. · The WHI evidence does not establish that menopausal hormone therapy extends human lifespan or reverses aging.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Clinical context does not provide individualized treatment advice and does not turn a symptom indication into a prevention claim. · Subgroup patterns may be imprecise or interaction-dependent and cannot create a general longevity indication. · A null overall mortality comparison is not evidence of lifespan extension or biological rejuvenation.

Funding and conflicts: NIH/NHLBI sponsored the WHI hormone trials; Wyeth-Ayerst donated study drugs. Regimen-specific disclosures remain visible.

Correction/retraction state: none

Connected reporting

Menopausal hormone therapy treats symptoms. WHI did not show a longevity benefit

Measured outcome: disease events, breast cancer and all-cause mortality

Released conclusion: WHI found a formulation-specific mix of benefits and harms, no overall 18-year mortality difference, and no basis for general longevity prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00000611

Identifier and correction state checked · projected from ninth-coverage-edition.json

peer-reviewed-meta-analysis · peer-reviewed

Cosmos Clinic Meta

DOI 10.1016/j.ajcnut.2023.12.011

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-meta-analysis
Study designEvidence synthesisrandomized trial substudy and program meta analysis
Population or modelMixed or synthesismultiple correlated randomized substudies measuring cognitive-test performance and DNA-methylation biomarkers
Population/model
573 clinic participants plus three correlated COSMOS cognitive substudies
Intervention and comparator
multivitamins; correlated randomized substudies
Duration
Not separately structured in this publication record
Measured outcome
global cognition, episodic memory, executive function, and attention

What the covered evidence found

COSMOS cognitive substudies reported small improvements in some cognitive-test scores, with mixed results across domains. · The three cognitive reports are directionally consistent analyses from one parent COSMOS program rather than three independent replications.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Test-score differences do not establish dementia prevention or preserved independent function. · Shared recruitment and program infrastructure limit independence.

Funding and conflicts: NIH and other support; Pfizer Consumer Healthcare/Haleon supplied some pills and packaging.

Correction/retraction state: none

Connected reporting

Multivitamins moved some tests and aging clocks. What does that mean?

Measured outcome: cognitive-test scores, word recall and DNA-methylation biomarkers

Released conclusion: COSMOS found small cognitive-test differences and modest movement in two DNA-methylation clocks; neither establishes dementia prevention or longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03035201 · NCT04582617

Identifier and correction state checked · projected from seventh-coverage-edition.json

systematic-review · peer-reviewed

Gallicchio Kalesan Sleep Mortality 2009

DOI 10.1111/j.1365-2869.2008.00732.x

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedsystematic-review
Study designEvidence synthesissystematic review and meta analysis
Population or modelAnimal modelmainly human observational evidence
Population/model
23 adult observational studies using self-reported duration
Intervention and comparator
sleep; mostly observational evidence
Duration
Not separately structured in this publication record
Measured outcome
all-cause mortality; cardiovascular mortality; cancer mortality

What the covered evidence found

In adult observational evidence, short or long self-reported duration and irregular-insufficient objective sleep patterns are associated with higher all-cause mortality than reference patterns. · The reviewed human evidence does not establish that changing sleep duration or regularity extends healthy-human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: observational evidence · self-reported sleep · heterogeneous duration categories · reverse causation · association is not causation · residual confounding · measurement differences · absence of a lifespan intervention trial is not proof no intervention could help

Funding and conflicts: paper disclosures to be shown

Correction/retraction state: none

Connected reporting

Sleep patterns are linked to healthy aging—but most evidence is observational

Measured outcome: mortality and frailty associations

Released conclusion: Duration, regularity and fragmentation carry health signals, but the featured studies do not show that changing one metric extends lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from third-coverage-edition.json

systematic-review-meta-analysis · peer-reviewed

Creatine Meta

DOI 10.2147/OAJSM.S123529

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedsystematic-review-meta-analysis
Study designEvidence synthesissystematic review meta analysis
Population or modelPeoplesystematic review plus randomized human trials
Population/model
22 trials; 721 participants
Intervention and comparator
creatine; trials and pooled evidence
Duration
Not separately structured in this publication record
Measured outcome
DXA lean tissue and chest/leg press strength

What the covered evidence found

Creatine plus resistance training produced modest pooled lean-tissue and strength gains versus training plus placebo. · The featured creatine evidence does not establish better independent function, healthspan, mortality or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Heterogeneous short trials; DXA lean tissue is sensitive to body water and is not direct function. · Trials measured muscle, bone, strength and safety markers, not longevity.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Applicable registry records: NCT01057680

Identifier and correction state checked · projected from fifth-coverage-edition.json

peer-reviewed-meta-analysis · peer-reviewed

Ctt Older Meta Analysis

PMID 30712900

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-meta-analysis
Study designEvidence synthesisindividual participant meta analysis
Population or modelPeoplerandomized human trials, subgroup analyses, extended follow-up, and individual-participant meta-analysis
Population/model
Participants in 28 randomized statin trials across age groups
Intervention and comparator
statins; trials and pooled evidence
Duration
Not separately structured in this publication record
Measured outcome
major vascular events and mortality

What the covered evidence found

PROSPER's primary-prevention subgroup and ALLHAT-LLT's older-adult analysis were neutral, while pooled evidence is clearer for older adults with established vascular disease.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: ALLHAT-LLT had crossover and modest LDL separation; subgroup and meta-analytic evidence do not replace an adequately powered dedicated trial.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Statin evidence changes with age, risk and prevention setting

Measured outcome: coronary and vascular events, stroke, mortality, cognition and cancer follow-up

Released conclusion: Evidence is clearer after vascular disease than for starting primary prevention after age 75, and it does not establish longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02099123 · NCT04262206

Identifier and correction state checked · projected from sixth-coverage-edition.json

primary-observational-meta-analysis · peer-reviewed

Cho et al. 2024 pooled cohort analysis

PMID 38329816

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-observational-meta-analysis
Study designEvidence synthesisprimary observational meta analysis
Population or modelPeopleHuman mortality · large observational cohorts
Population/model
Adult cigarette-smoking status, cessation timing, all-cause and cause-specific mortality, and modeled survival in the included national cohorts
Intervention and comparator
cigarette smoking cessation; observational current and former cigarette smokers compared with never smokers; cessation timing compared with continued smoking
Duration
Not separately structured in this publication record
Measured outcome
Adult cigarette-smoking status, cessation timing, all-cause and cause-specific mortality, and modeled survival in the included national cohorts

What the covered evidence found

Cho pooled 1.48 million adults in four countries and observed 122,697 deaths · Current-smoker hazard ratios were 2.8 for women and 2.7 for men; survival from age 40 to 79 was shorter by 12 and 13 years · Lower excess-mortality associations appeared within fewer than three years; estimates after ten or more years approached never-smoker survival · Government and academic support was reported and author disclosure forms were filed · Self-report, residual confounding and generalizability limits remain

What it does not establish

A universal population estimate · An individual outcome · A product prescription · A claim of no conflicts · Proof of an exact causal effect

Limitations: Cohort and era heterogeneity · Adjusted observational result · No cessation-method comparison · Forms are not itemized in accessible primary metadata · Observational evidence

Funding and conflicts: Canadian Institutes of Health Research FDN-154277

Correction/retraction state: none-linked-as-of-2026-08-27

Connected reporting

Stopping smoking was associated with lower mortality at every age studied

Measured outcome: all-cause and cause-specific mortality plus modeled survival

Released conclusion: Current cigarette smoking was associated with roughly three times the mortality of never smoking; stopping was associated with lower excess mortality at every age studied.

Boundary: The analyses did not establish an exact causal effect for every subgroup, forecast an individual lifespan, or compare cessation treatments.

Identifier and correction state checked · projected from nineteenth-coverage-claim-map.json

systematic-review · peer-reviewed

Nmn Meta Analysis

PMID 39531138

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedsystematic-review
Study designEvidence synthesissystematic review and meta analysis
Population or modelPeopleearly randomized human biomarker and short-term physiological evidence; no lifespan evidence
Population/model
8 trials and 342 participants
Intervention and comparator
NAD biology; small trials
Duration
Not separately structured in this publication record
Measured outcome
glucose and lipid outcomes

What the covered evidence found

No featured NAD-precursor evidence establishes longer healthy-human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Compounds, routes and formulations are not interchangeable.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

NAD precursors raise some metabolites; human longevity benefits remain unproven

Measured outcome: metabolites, physiology and short-term function

Released conclusion: Small trials show target engagement, not broad clinical, healthspan or lifespan benefit—and products and routes are not interchangeable.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02835664 · NCT02921659 · NCT04823260

Identifier and correction state checked · projected from fourth-coverage-edition.json

peer-reviewed-systematic-review · peer-reviewed

Passive Heating Rct Review

PMID 41049507

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-systematic-review
Study designEvidence synthesissystematic review of randomized trials
Population or modelPeoplelong prospective human cohort association, with later randomized passive-heating evidence limited to short-term surrogate outcomes rather than mortality
Population/model
Participants in 20 randomized passive-heating trials
Intervention and comparator
habitual sauna use; prospective cohort by self-reported frequency
Duration
Not separately structured in this publication record
Measured outcome
Short-term surrogate cardiometabolic and vascular outcomes, not mortality

What the covered evidence found

A 2025 systematic review of 20 randomized passive-heating trials did not find pooled effects for most short-term surrogate outcomes and did not test mortality.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to the named study design, population, exposure and measured endpoint; it must not be generalized into proof of disease prevention, rejuvenation, healthspan improvement or longer life.

Funding and conflicts: The Finnish cohort paper reported public and foundation support and no conflicts of interest. Its observational design, self-reported baseline sauna exposure and residual confounding remain more important interpretive limits than sponsorship.

Correction/retraction state: none

Connected reporting

Sauna use was associated with lower mortality—not proven to extend life

Measured outcome: cardiovascular and all-cause mortality association

Released conclusion: One Finnish male cohort linked frequent sauna use with lower mortality. The design cannot show that sauna caused longer life, and randomized evidence has not tested that endpoint.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from fourteenth-coverage-edition.json

Observational study

7 covered publications

peer-reviewed-primary-cohort · peer-reviewed

Sauna Finnish Cohort

DOI 10.1001/jamainternmed.2014.8187

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-cohort
Study designObservational studyprospective observational cohort
Population or modelPeoplelong prospective human cohort association, with later randomized passive-heating evidence limited to short-term surrogate outcomes rather than mortality
Population/model
2,315 eastern Finnish men age 42 to 60 at baseline
Intervention and comparator
habitual sauna use; prospective cohort by self-reported frequency
Duration
Not separately structured in this publication record
Measured outcome
Sudden cardiac death, fatal coronary heart disease, fatal cardiovascular disease and all-cause mortality over median 20.7 years

What the covered evidence found

The Finnish cohort followed 2,315 men who were 42 to 60 years old at baseline for a median 20.7 years. · During follow-up the cohort recorded 190 sudden cardiac deaths, 281 fatal coronary heart disease events, 407 fatal cardiovascular disease events and 929 all-cause deaths. · Compared with one sauna session per week, four to seven sessions per week were associated with a sudden-cardiac-death hazard ratio of 0.37 with a 95% confidence interval of 0.18 to 0.75. · The sauna result is an observational association and cannot establish that sauna caused lower mortality or that the estimate applies beyond this selected male Finnish cohort.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to the named study design, population, exposure and measured endpoint; it must not be generalized into proof of disease prevention, rejuvenation, healthspan improvement or longer life.

Funding and conflicts: The Finnish cohort paper reported public and foundation support and no conflicts of interest. Its observational design, self-reported baseline sauna exposure and residual confounding remain more important interpretive limits than sponsorship.

Correction/retraction state: none

Connected reporting

Sauna use was associated with lower mortality—not proven to extend life

Measured outcome: cardiovascular and all-cause mortality association

Released conclusion: One Finnish male cohort linked frequent sauna use with lower mortality. The design cannot show that sauna caused longer life, and randomized evidence has not tested that endpoint.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from fourteenth-coverage-edition.json

peer-reviewed-false-positive-analysis · peer-reviewed

pmid 21788129

DOI 10.1016/j.ejca.2011.06.055

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-false-positive-analysis
Study designObservational studypeer reviewed false positive analysis
Population or modelPeopleHuman prostate-cancer mortality and diagnosis · long randomized screening follow-up
Population/model
42,376 men age 55–74 in ERSPC Rotterdam; primary analysis in 34,831 men age 55–69
Intervention and comparator
Invitation to PSA-based screening about every four years versus control
Duration
Median 21-year Rotterdam follow-up
Measured outcome
excess diagnosis and false positives

What the covered evidence found

Rotterdam reported 57 excess prostate-cancer diagnoses per 1,000 randomized to screening; across five ERSPC centers, 17.8% of screened men had at least one false positive.

What it does not establish

Does not mean every additional diagnosis is harmful or that cancer-specific benefit erases urinary, sexual and other harms.

Limitations: Excess diagnosis is not identical to overdiagnosis in every case; biopsy and treatment harms need separate evidence.

Funding and conflicts: Dutch Cancer Society, Netherlands Organisation for Health Research and Development, Dutch Cancer Research Foundation, and an unconditional Beckman-Coulter-Hybritech grant; focal paper reports no author conflicts.

Correction/retraction state: none-found

Connected reporting

PSA screening lowered prostate-cancer mortality—and increased diagnoses

Measured outcome: prostate-cancer mortality, metastasis and diagnoses

Released conclusion: In the primary age group, prostate-cancer mortality was lower with screening (RR 0.73), as was metastatic disease (RR 0.67). Screening also produced 57 excess prostate-cancer diagnoses per 1,000 men randomized.

Boundary: An all-cause survival benefit or favorable balance for every individual.

Identifier and correction state checked · projected from sixteenth-coverage-claim-map.json

peer-reviewed-natural-experiment · peer-reviewed

Live Zoster Dementia Wales

DOI 10.1038/s41586-025-08800-x

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-natural-experiment
Study designObservational studyregression discontinuity natural experiment
Population or modelPeoplestrong randomized shingles-prevention evidence with emerging observational and quasi-experimental dementia evidence
Population/model
282,541 adults around the September 2, 1933 Welsh vaccine-eligibility birth-date cutoff
Intervention and comparator
shingles vaccine; randomized and non-randomized evidence
Duration
Not separately structured in this publication record
Measured outcome
new recorded dementia diagnosis over seven years after eligibility for live-attenuated zoster vaccine

What the covered evidence found

In the Welsh eligibility-cutoff natural experiment, receiving live-attenuated zoster vaccine was estimated to reduce a new dementia diagnosis over seven years by 3.5 percentage points (95% CI 0.6–7.1), a 20.0% relative reduction. · Current evidence does not establish recombinant zoster vaccination as a causal dementia-prevention treatment or an FDA-approved dementia indication. · The featured shingles-vaccine studies do not establish slower biological aging, greater healthspan or longer human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The study was quasi-experimental rather than randomized, used the discontinued live vaccine in people around age 79–80, and relied on recorded diagnoses. · The dementia studies are observational or quasi-experimental and involve different vaccine formulations; a randomized dementia endpoint has not been established. · Disease prevention and diagnosis timing cannot be substituted for a measured lifespan outcome.

Funding and conflicts: GSK funded ZOE-50. The recombinant-dementia EHR study had NIHR/Wellcome/JDRF support and disclosed one author's GSK consultancy and Oxford–GSK role; GSK was reported uninvolved. The Welsh study reported public and philanthropic grants and no competing interests.

Correction/retraction state: none

Connected reporting

Shingles vaccines prevent shingles. Dementia evidence remains non-randomized

Measured outcome: herpes-zoster disease and recorded dementia diagnoses

Released conclusion: Randomized trials established shingles prevention. Dementia findings come from observational and quasi-experimental studies and do not prove prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01165177

Identifier and correction state checked · projected from tenth-coverage-edition.json

peer-reviewed-observational · peer-reviewed

Recombinant Zoster Dementia Ehr

DOI 10.1038/s41591-024-03201-5

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-observational
Study designObservational studyobservational natural experiment
Population or modelPeoplestrong randomized shingles-prevention evidence with emerging observational and quasi-experimental dementia evidence
Population/model
two propensity-matched U.S. electronic-health-record cohorts of 103,837 vaccinated adults each
Intervention and comparator
shingles vaccine; randomized and non-randomized evidence
Duration
Not separately structured in this publication record
Measured outcome
recorded dementia diagnoses during up to six years after live or recombinant zoster vaccination

What the covered evidence found

A matched U.S. health-record comparison associated the recombinant rather than live zoster-vaccine era with 17% more dementia-diagnosis-free time, or 164 additional diagnosis-free days among people later diagnosed. · Current evidence does not establish recombinant zoster vaccination as a causal dementia-prevention treatment or an FDA-approved dementia indication. · The featured shingles-vaccine studies do not establish slower biological aging, greater healthspan or longer human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This observational comparison cannot establish causality, diagnoses were not independently validated, and unmeasured differences between vaccine eras may remain. · The dementia studies are observational or quasi-experimental and involve different vaccine formulations; a randomized dementia endpoint has not been established. · Disease prevention and diagnosis timing cannot be substituted for a measured lifespan outcome.

Funding and conflicts: GSK funded ZOE-50. The recombinant-dementia EHR study had NIHR/Wellcome/JDRF support and disclosed one author's GSK consultancy and Oxford–GSK role; GSK was reported uninvolved. The Welsh study reported public and philanthropic grants and no competing interests.

Correction/retraction state: none

Connected reporting

Shingles vaccines prevent shingles. Dementia evidence remains non-randomized

Measured outcome: herpes-zoster disease and recorded dementia diagnoses

Released conclusion: Randomized trials established shingles prevention. Dementia findings come from observational and quasi-experimental studies and do not prove prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01165177

Identifier and correction state checked · projected from tenth-coverage-edition.json

primary-paper · peer-reviewed

Mesa Sleep Regularity Mortality

DOI 10.1111/jsr.14048

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designObservational studyprospective observational cohort
Population or modelPeoplemainly human observational evidence
Population/model
1,759 diverse US adults with seven-day actigraphy
Intervention and comparator
sleep; mostly observational evidence
Duration
Not separately structured in this publication record
Measured outcome
all-cause mortality association

What the covered evidence found

In adult observational evidence, short or long self-reported duration and irregular-insufficient objective sleep patterns are associated with higher all-cause mortality than reference patterns. · The reviewed human evidence does not establish that changing sleep duration or regularity extends healthy-human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: cluster combines regularity and duration · residual confounding · reverse causation · one baseline sleep window · association is not causation · measurement differences · absence of a lifespan intervention trial is not proof no intervention could help

Funding and conflicts: paper disclosures checked; authors declared no conflicts

Correction/retraction state: none

Connected reporting

Sleep patterns are linked to healthy aging—but most evidence is observational

Measured outcome: mortality and frailty associations

Released conclusion: Duration, regularity and fragmentation carry health signals, but the featured studies do not show that changing one metric extends lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from third-coverage-edition.json

primary-observational-report · peer-reviewed

Jha et al. 2013 linked NHIS mortality analysis

PMID 23343063

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-observational-report
Study designObservational studyprimary observational report
Population or modelPeopleHuman mortality · large observational cohorts
Population/model
Adult cigarette-smoking status, cessation timing, all-cause and cause-specific mortality, and modeled survival in the included national cohorts
Intervention and comparator
cigarette smoking cessation; observational current and former cigarette smokers compared with never smokers; cessation timing compared with continued smoking
Duration
Not separately structured in this publication record
Measured outcome
Adult cigarette-smoking status, cessation timing, all-cause and cause-specific mortality, and modeled survival in the included national cohorts

What the covered evidence found

Jha analyzed 202,248 US adults age 25+ with mortality linkage · Current-versus-never mortality hazard ratios were about 3 and survival estimates differed by more than ten years · Earlier cessation was associated with larger survival gains compared with continued smoking · Government and academic support was reported and author disclosure forms were filed · Self-report, residual confounding and generalizability limits remain

What it does not establish

A randomized causal effect · An individualized forecast · Guaranteed years gained · A claim of no conflicts · Proof of an exact causal effect

Limitations: Observational NHIS cohort with self-reported smoking status · Adjusted population association · Modeled observational comparison · Forms are not itemized in accessible primary metadata · Observational evidence

Funding and conflicts: UK MRC, NIH Fogarty and CIHR support reported in primary metadata

Correction/retraction state: none-linked-as-of-2026-08-27

Connected reporting

Stopping smoking was associated with lower mortality at every age studied

Measured outcome: all-cause and cause-specific mortality plus modeled survival

Released conclusion: Current cigarette smoking was associated with roughly three times the mortality of never smoking; stopping was associated with lower excess mortality at every age studied.

Boundary: The analyses did not establish an exact causal effect for every subgroup, forecast an individual lifespan, or compare cessation treatments.

Identifier and correction state checked · projected from nineteenth-coverage-claim-map.json

regulator-safety-warning · publication record

Fda Rsv Gbs Surveillance

Source fda-rsv-gbs-warning-2025

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepublication recordregulator-safety-warning
Study designObservational studypostauthorization observational safety review
Population or modelPeoplethree large randomized product-specific trials plus maturing durability and postauthorization safety evidence
Population/model
U.S. Medicare beneficiaries age 65 or older receiving Abrysvo or Arexvy
Intervention and comparator
RSV vaccines; three randomized vaccine trials
Duration
Not separately structured in this publication record
Measured outcome
postmarketing Guillain–Barré syndrome signal and labeling warning

What the covered evidence found

FDA required Guillain–Barré syndrome warnings for Arexvy and Abrysvo after observational estimates of about 7 and 9 excess cases per million doses, respectively, while stating that available evidence was insufficient to establish causality.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Postmarketing observational estimates have residual uncertainty, apply to the named products and surveillance population, and should not be transferred to mResvia.

Funding and conflicts: The Arexvy, Abrysvo and mResvia pivotal trials were funded by GSK, Pfizer and Moderna, respectively; current guidance and postauthorization safety context come from CDC and FDA.

Correction/retraction state: none

Connected reporting

RSV vaccines reduce respiratory disease. Separate trials cannot rank them

Measured outcome: RSV lower-respiratory disease or illness, acute respiratory disease and safety

Released conclusion: Arexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT04886596 · NCT05035212 · NCT05127434

Identifier and correction state checked · projected from tenth-coverage-edition.json

Other human evidence

33 covered publications

peer-reviewed-secondary · peer-reviewed

Achieve Secondary

DOI 10.1002/alz.70156

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-secondary
Study designOther human evidencesecondary analysis
Population or modelAnimal modelrandomized human evidence with secondary subgroup analysis
Population/model
ACHIEVE participants stratified by predicted cognitive risk
Intervention and comparator
hearing; randomized trial with subgroup signals
Duration
Not separately structured in this publication record
Measured outcome
modeled cognitive-change heterogeneity

What the covered evidence found

Prespecified recruitment-source and later modeled-risk analyses found larger signals among higher-risk participants.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Subgroup and secondary analyses do not override the null total-cohort primary endpoint.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Hearing intervention did not slow cognitive decline across the full ACHIEVE trial

Measured outcome: three-year standardized global-cognition change

Released conclusion: The three-year trial was null across its full cohort. Signals in higher-risk groups need confirmation and do not establish dementia prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03243422

Identifier and correction state checked · projected from fifth-coverage-edition.json

correction-notice · peer-reviewed

Liftmor Erratum

DOI 10.1002/jbmr.3659

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedcorrection-notice
Study designOther human evidencepublished correction
Population or modelPeoplesmall randomized human BMD and function evidence with bounded vertebral-safety follow-up and a published correction
Population/model
the published LIFTMOR primary report and corrected table values
Intervention and comparator
LIFTMOR; small supervised randomized trial
Duration
Not separately structured in this publication record
Measured outcome
table-heading and calcium-intake-change corrections

What the covered evidence found

The LIFTMOR erratum corrected table headings and the sign of calcium-intake change; it did not create or reverse a bone or fracture outcome.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The correction must remain visible without implying that unaffected outcomes were reanalyzed or reversed.

Funding and conflicts: Griffith University and The Bone Clinic affiliations and later commercial translation require visible context; marketing is not efficacy evidence.

Correction/retraction state: correction-notice

Connected reporting

LIFTMOR improved bone density in a small supervised trial—not fracture prevention

Measured outcome: bone density, strength and functional measures

Released conclusion: LIFTMOR found BMD and function gains in a small, screened, closely supervised trial—not fracture prevention or proof that unsupervised heavy training is safe.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from ninth-coverage-edition.json

peer-reviewed-secondary-analysis · peer-reviewed

Active Dementia Claims

DOI 10.1002/trc2.70197

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-secondary-analysis
Study designOther human evidenceclaims linked secondary analysis
Population or modelPeoplerandomized trained-ability evidence plus long-term function, mortality and contested claims-based dementia analyses
Population/model
2,021 ACTIVE participants enrolled in traditional Medicare at baseline
Intervention and comparator
cognitive training; randomized trial plus disputed secondary analysis
Duration
Not separately structured in this publication record
Measured outcome
claims-diagnosed ADRD in randomized arms and post-randomization booster subgroups

What the covered evidence found

A claims-linked analysis reported HR 0.75 only among speed trainees who completed boosters; randomized arms were null and non-booster speed trainees had HR 1.01.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Booster completion was post-randomization and the claims-based subgroup result is not a randomized prevention estimate.

Funding and conflicts: NIH-supported trial and follow-ups; the 20-year mortality report declared no conflicts, while commercial descendants are not evidence for the studied protocol.

Correction/retraction state: none

Connected reporting

Cognitive training improved practiced skills—not survival or proven dementia prevention

Measured outcome: trained abilities, daily function, all-cause mortality and claims-diagnosed dementia

Released conclusion: ACTIVE supports trained-ability gains and some function signals, found no mortality benefit, and leaves a claims-based dementia subgroup methodologically disputed.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00298558

Identifier and correction state checked · projected from eighth-coverage-edition.json

peer-reviewed-critique · peer-reviewed

Active Dementia Critique

DOI 10.1002/trc2.70280

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-critique
Study designOther human evidencepublished methodological critique
Population or modelPeoplerandomized trained-ability evidence plus long-term function, mortality and contested claims-based dementia analyses
Population/model
methodological assessment of the ACTIVE claims-linked dementia subgroup analysis
Intervention and comparator
cognitive training; randomized trial plus disputed secondary analysis
Duration
Not separately structured in this publication record
Measured outcome
comparability, selection, claims diagnosis, prespecification and multiplicity limitations

What the covered evidence found

The ACTIVE booster subgroup result is contested over comparability, selection, claims diagnosis, lack of prespecification and multiplicity; the authors published a response.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The published critique and response must be presented together; confidence in a prevention claim remains low.

Funding and conflicts: NIH-supported trial and follow-ups; the 20-year mortality report declared no conflicts, while commercial descendants are not evidence for the studied protocol.

Correction/retraction state: none

Connected reporting

Cognitive training improved practiced skills—not survival or proven dementia prevention

Measured outcome: trained abilities, daily function, all-cause mortality and claims-diagnosed dementia

Released conclusion: ACTIVE supports trained-ability gains and some function signals, found no mortality benefit, and leaves a claims-based dementia subgroup methodologically disputed.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00298558

Identifier and correction state checked · projected from eighth-coverage-edition.json

peer-reviewed-response · peer-reviewed

Active Dementia Response

DOI 10.1002/trc2.70290

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-response
Study designOther human evidencepublished author response
Population or modelPeoplerandomized trained-ability evidence plus long-term function, mortality and contested claims-based dementia analyses
Population/model
author response concerning the ACTIVE claims-linked dementia subgroup analysis
Intervention and comparator
cognitive training; randomized trial plus disputed secondary analysis
Duration
Not separately structured in this publication record
Measured outcome
response to published methodological criticism

What the covered evidence found

The ACTIVE booster subgroup result is contested over comparability, selection, claims diagnosis, lack of prespecification and multiplicity; the authors published a response.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The published critique and response must be presented together; confidence in a prevention claim remains low.

Funding and conflicts: NIH-supported trial and follow-ups; the 20-year mortality report declared no conflicts, while commercial descendants are not evidence for the studied protocol.

Correction/retraction state: none

Connected reporting

Cognitive training improved practiced skills—not survival or proven dementia prevention

Measured outcome: trained abilities, daily function, all-cause mortality and claims-diagnosed dementia

Released conclusion: ACTIVE supports trained-ability gains and some function signals, found no mortality benefit, and leaves a claims-based dementia subgroup methodologically disputed.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00298558

Identifier and correction state checked · projected from eighth-coverage-edition.json

peer-reviewed · peer-reviewed

Ocampo 2016 Oskm

DOI 10.1016/j.cell.2016.11.052

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed
Study designOther human evidencestudy publication
Population or modelAnimal modelMaturity described in linked reporting
Population/model
mice
Intervention and comparator
partial reprogramming; no results yet
Duration
Not separately structured in this publication record
Measured outcome
planned safety, dose-limiting toxicity, laboratory and eye measures; no posted results

What the covered evidence found

A recruiting Phase 1 eye study asks whether ER-100 can be administered safely. It has no posted human efficacy results and does not test lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: not separately structured

Connected reporting

Partial-reprogramming trial is testing eye-treatment safety—not human rejuvenation

Measured outcome: planned safety, dose-limiting toxicity, laboratory and eye measures; no posted results

Released conclusion: A recruiting Phase 1 eye study asks whether ER-100 can be administered safely. It has no posted human efficacy results and does not test lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT07290244

Identifier and correction state checked · projected from first-coverage-pilot.json

primary-paper · peer-reviewed

Pmid 30616998 Covered Publication

DOI 10.1016/j.ebiom.2018.12.052

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designOther human evidenceprimary paper
Population or modelMixed or synthesisearly human feasibility and biomarker evidence
Population/model
35 people across three small studies of pulmonary fibrosis or diabetic kidney disease
Intervention and comparator
senolytics; small pilots
Duration
Not separately structured in this publication record
Measured outcome
feasibility, adverse events, function and tissue biomarkers

What the covered evidence found

Three disease-specific pilot studies do not establish rejuvenation, healthy-person benefit, healthspan or lifespan extension.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Human senolytic studies remain small safety and feasibility pilots

Measured outcome: feasibility, adverse events, function and tissue biomarkers

Released conclusion: Three disease-specific pilot studies do not establish rejuvenation, healthy-person benefit, healthspan or lifespan extension.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from second-coverage-edition.json

primary-paper · peer-reviewed

Pmid 31542391 Covered Publication

DOI 10.1016/j.ebiom.2019.08.069

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designOther human evidenceprimary paper
Population or modelMixed or synthesisearly human feasibility and biomarker evidence
Population/model
35 people across three small studies of pulmonary fibrosis or diabetic kidney disease
Intervention and comparator
senolytics; small pilots
Duration
Not separately structured in this publication record
Measured outcome
feasibility, adverse events, function and tissue biomarkers

What the covered evidence found

Three disease-specific pilot studies do not establish rejuvenation, healthy-person benefit, healthspan or lifespan extension.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: corrected

Connected reporting

Human senolytic studies remain small safety and feasibility pilots

Measured outcome: feasibility, adverse events, function and tissue biomarkers

Released conclusion: Three disease-specific pilot studies do not establish rejuvenation, healthy-person benefit, healthspan or lifespan extension.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from second-coverage-edition.json

primary-paper · peer-reviewed

Pmid 36857968 Covered Publication

DOI 10.1016/j.ebiom.2023.104481

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designOther human evidenceprimary paper
Population or modelMixed or synthesisearly human feasibility and biomarker evidence
Population/model
35 people across three small studies of pulmonary fibrosis or diabetic kidney disease
Intervention and comparator
senolytics; small pilots
Duration
Not separately structured in this publication record
Measured outcome
feasibility, adverse events, function and tissue biomarkers

What the covered evidence found

Three disease-specific pilot studies do not establish rejuvenation, healthy-person benefit, healthspan or lifespan extension.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Human senolytic studies remain small safety and feasibility pilots

Measured outcome: feasibility, adverse events, function and tissue biomarkers

Released conclusion: Three disease-specific pilot studies do not establish rejuvenation, healthy-person benefit, healthspan or lifespan extension.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from second-coverage-edition.json

peer-reviewed-primary-human-physiology · peer-reviewed

Cold Winter Swimmers

DOI 10.1016/j.xcrm.2021.100408

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-human-physiology
Study designOther human evidencesmall cross sectional human physiology study
Population or modelPeoplesmall human physiology study measuring brown-fat activation, thermogenesis and laboratory markers rather than disease, function, healthspan or longevity outcomes
Population/model
Eight healthy young male winter swimmers and eight matched men; principal analysis seven versus eight
Intervention and comparator
habitual winter swimming and cold challenge; cross-sectional swimmer versus matched comparison group
Duration
Not separately structured in this publication record
Measured outcome
Brown-fat activity, thermogenesis and laboratory physiology measures

What the covered evidence found

The cold study compared eight healthy young male winter swimmers with eight matched men, and its principal analysis used seven swimmers because one was excluded. · Seven of the eight winter swimmers also used sauna, so the study could not isolate cold-water exposure from their broader habits. · The study measured brown-fat activity, cold-induced thermogenesis and laboratory physiology markers, not disease, function, healthspan, mortality or lifespan. · Reported 24-hour energy-expenditure estimates were extrapolated from a 30-minute cold-exposure measurement rather than observed over a full day. · The cross-sectional study cannot establish that winter swimming caused the measured differences or that cold exposure produces clinical or longevity benefits.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to the named study design, population, exposure and measured endpoint; it must not be generalized into proof of disease prevention, rejuvenation, healthspan improvement or longer life.

Funding and conflicts: The cold-exposure study reported Czech public research support and no competing interests. Seven of eight winter swimmers also used sauna, and the small selected sample makes attribution and generalization especially uncertain.

Correction/retraction state: none

Connected reporting

Cold-water studies measure thermogenesis—not longer life

Measured outcome: brown-fat activity and thermogenesis

Released conclusion: A small study of young male winter swimmers found physiology differences. It did not test disease, function, healthspan or lifespan, and it cannot show that cold exposure caused the findings.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03095846 · NCT03096535

Identifier and correction state checked · projected from fourteenth-coverage-edition.json

primary-paper · peer-reviewed

Pmid 31303390 Covered Publication

DOI 10.1016/S2213-8587(19)30151-2

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designOther human evidenceprimary paper
Population or modelPeoplerandomized human trial; indirect for longevity
Population/model
218 healthy, non-obese adults age 21–51
Intervention and comparator
calorie restriction; randomized trial
Duration
Not separately structured in this publication record
Measured outcome
metabolism, cardiometabolic risk factors and DNA-methylation biomarkers

What the covered evidence found

A randomized trial found selected cardiometabolic improvements, while aging-biomarker results were mixed and lifespan was not measured.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

CALERIE tested calorie restriction for two years—not human lifespan

Measured outcome: metabolism, cardiometabolic risk factors and DNA-methylation biomarkers

Released conclusion: A randomized trial found selected cardiometabolic improvements, while aging-biomarker results were mixed and lifespan was not measured.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00427193

Identifier and correction state checked · projected from second-coverage-edition.json

peer-reviewed · peer-reviewed

Lu 2020 Osk

DOI 10.1038/s41586-020-2975-4

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed
Study designOther human evidencestudy publication
Population or modelAnimal modelMaturity described in linked reporting
Population/model
mice
Intervention and comparator
partial reprogramming; no results yet
Duration
Not separately structured in this publication record
Measured outcome
planned safety, dose-limiting toxicity, laboratory and eye measures; no posted results

What the covered evidence found

A recruiting Phase 1 eye study asks whether ER-100 can be administered safely. It has no posted human efficacy results and does not test lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: not separately structured

Connected reporting

Partial-reprogramming trial is testing eye-treatment safety—not human rejuvenation

Measured outcome: planned safety, dose-limiting toxicity, laboratory and eye measures; no posted results

Released conclusion: A recruiting Phase 1 eye study asks whether ER-100 can be administered safely. It has no posted human efficacy results and does not test lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT07290244

Identifier and correction state checked · projected from first-coverage-pilot.json

primary-paper · peer-reviewed

Pmid 36277076 Covered Publication

DOI 10.1038/s43587-022-00248-2

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designOther human evidenceprimary paper
Population or modelCells or tissueresearch biomarker; clinical utility not established
Population/model
Human tissue datasets and longitudinal cohorts used to train or validate different clocks
Intervention and comparator
epigenetic clocks; human validation evidence
Duration
Not separately structured in this publication record
Measured outcome
DNA-methylation biomarker estimates and cohort associations

What the covered evidence found

Different clocks target different constructs. A score is not a diagnosis, and changing it does not prove longer life.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

What an epigenetic clock can—and cannot—tell you

Measured outcome: DNA-methylation biomarker estimates and cohort associations

Released conclusion: Different clocks target different constructs. A score is not a diagnosis, and changing it does not prove longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from second-coverage-edition.json

secondary-analysis · peer-reviewed

Pmid 37118425 Covered Publication

DOI 10.1038/s43587-022-00357-y

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedsecondary-analysis
Study designOther human evidencesecondary analysis
Population or modelPeoplerandomized human trial; indirect for longevity · research biomarker; clinical utility not established
Population/model
218 healthy, non-obese adults age 21–51
Intervention and comparator
calorie restriction; randomized trial · epigenetic clocks; human validation evidence
Duration
Not separately structured in this publication record
Measured outcome
metabolism, cardiometabolic risk factors and DNA-methylation biomarkers

What the covered evidence found

A randomized trial found selected cardiometabolic improvements, while aging-biomarker results were mixed and lifespan was not measured. · Different clocks target different constructs. A score is not a diagnosis, and changing it does not prove longer life.

What it does not establish

CALERIE tested calorie restriction for two years—not human lifespan · What an epigenetic clock can—and cannot—tell you

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: corrected

Connected reporting

CALERIE tested calorie restriction for two years—not human lifespan

Measured outcome: metabolism, cardiometabolic risk factors and DNA-methylation biomarkers

Released conclusion: A randomized trial found selected cardiometabolic improvements, while aging-biomarker results were mixed and lifespan was not measured.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

What an epigenetic clock can—and cannot—tell you

Measured outcome: DNA-methylation biomarker estimates and cohort associations

Released conclusion: Different clocks target different constructs. A score is not a diagnosis, and changing it does not prove longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00427193

Identifier and correction state checked · projected from second-coverage-edition.json

peer-reviewed-follow-up · peer-reviewed

Active Mortality

DOI 10.1093/aje/kwae381

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-follow-up
Study designOther human evidencelinked long term follow up
Population or modelPeoplerandomized trained-ability evidence plus long-term function, mortality and contested claims-based dementia analyses
Population/model
2,802 ACTIVE participants with mortality follow-up through 2019
Intervention and comparator
cognitive training; randomized trial plus disputed secondary analysis
Duration
Not separately structured in this publication record
Measured outcome
all-cause mortality by randomized training arm

What the covered evidence found

The 20-year ACTIVE mortality analysis found no significant effect of memory, reasoning or speed training on all-cause mortality.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The mortality analysis does not determine every possible health effect of cognitive training.

Funding and conflicts: NIH-supported trial and follow-ups; the 20-year mortality report declared no conflicts, while commercial descendants are not evidence for the studied protocol.

Correction/retraction state: none

Connected reporting

Cognitive training improved practiced skills—not survival or proven dementia prevention

Measured outcome: trained abilities, daily function, all-cause mortality and claims-diagnosed dementia

Released conclusion: ACTIVE supports trained-ability gains and some function signals, found no mortality benefit, and leaves a claims-based dementia subgroup methodologically disputed.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00298558

Identifier and correction state checked · projected from eighth-coverage-edition.json

primary-paper · peer-reviewed

Pmid 26187233 Covered Publication

DOI 10.1093/gerona/glv057

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designOther human evidenceprimary paper
Population or modelPeoplerandomized human trial; indirect for longevity
Population/model
218 healthy, non-obese adults age 21–51
Intervention and comparator
calorie restriction; randomized trial
Duration
Not separately structured in this publication record
Measured outcome
metabolism, cardiometabolic risk factors and DNA-methylation biomarkers

What the covered evidence found

A randomized trial found selected cardiometabolic improvements, while aging-biomarker results were mixed and lifespan was not measured.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

CALERIE tested calorie restriction for two years—not human lifespan

Measured outcome: metabolism, cardiometabolic risk factors and DNA-methylation biomarkers

Released conclusion: A randomized trial found selected cardiometabolic improvements, while aging-biomarker results were mixed and lifespan was not measured.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00427193

Identifier and correction state checked · projected from second-coverage-edition.json

peer-reviewed · peer-reviewed

Exercise Frailty Review

DOI 10.1123/jpah.2020-0323

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed
Study designOther human evidencestudy publication
Population or modelPeopleMaturity described in linked reporting
Population/model
humans
Intervention and comparator
exercise; mature randomized evidence
Duration
Not separately structured in this publication record
Measured outcome
mobility, function, frailty, falls and all-cause mortality

What the covered evidence found

Human trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: not separately structured

Connected reporting

Exercise has strong evidence for function—not proof of slower biological aging

Measured outcome: mobility, function, frailty, falls and all-cause mortality

Released conclusion: Human trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01072500

Identifier and correction state checked · projected from first-coverage-pilot.json

peer-reviewed · peer-reviewed

Generation 100

DOI 10.1136/bmj.m3485

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed
Study designOther human evidencestudy publication
Population or modelPeopleMaturity described in linked reporting
Population/model
humans
Intervention and comparator
exercise; mature randomized evidence
Duration
Not separately structured in this publication record
Measured outcome
mobility, function, frailty, falls and all-cause mortality

What the covered evidence found

Human trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: not separately structured

Connected reporting

Exercise has strong evidence for function—not proof of slower biological aging

Measured outcome: mobility, function, frailty, falls and all-cause mortality

Released conclusion: Human trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01072500

Identifier and correction state checked · projected from first-coverage-pilot.json

primary-paper · peer-reviewed

Pmid 24138928 Covered Publication

DOI 10.1186/gb-2013-14-10-r115

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designOther human evidenceprimary paper
Population or modelCells or tissueresearch biomarker; clinical utility not established
Population/model
Human tissue datasets and longitudinal cohorts used to train or validate different clocks
Intervention and comparator
epigenetic clocks; human validation evidence
Duration
Not separately structured in this publication record
Measured outcome
DNA-methylation biomarker estimates and cohort associations

What the covered evidence found

Different clocks target different constructs. A score is not a diagnosis, and changing it does not prove longer life.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

What an epigenetic clock can—and cannot—tell you

Measured outcome: DNA-methylation biomarker estimates and cohort associations

Released conclusion: Different clocks target different constructs. A score is not a diagnosis, and changing it does not prove longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from second-coverage-edition.json

primary-paper · peer-reviewed

Pmid 35029144 Covered Publication

DOI 10.7554/eLife.73420

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designOther human evidenceprimary paper
Population or modelCells or tissueresearch biomarker; clinical utility not established
Population/model
Human tissue datasets and longitudinal cohorts used to train or validate different clocks
Intervention and comparator
epigenetic clocks; human validation evidence
Duration
Not separately structured in this publication record
Measured outcome
DNA-methylation biomarker estimates and cohort associations

What the covered evidence found

Different clocks target different constructs. A score is not a diagnosis, and changing it does not prove longer life.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

What an epigenetic clock can—and cannot—tell you

Measured outcome: DNA-methylation biomarker estimates and cohort associations

Released conclusion: Different clocks target different constructs. A score is not a diagnosis, and changing it does not prove longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from second-coverage-edition.json

peer-reviewed-primary-human-biomarker · peer-reviewed

Hbot Aging Biomarkers

DOI 10.18632/aging.202188

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-human-biomarker
Study designOther human evidencesingle arm pre post human biomarker study
Population or modelPeoplesmall uncontrolled human biomarker study in selected blood-cell subtypes, without a clinical aging, healthspan or lifespan endpoint
Population/model
Thirty healthy adults age 64 or older completed the intervention; smaller analytic subsets for telomere and senescence measures
Intervention and comparator
supervised hyperbaric-oxygen research program; single-arm pre/post study without a control
Duration
Not separately structured in this publication record
Measured outcome
Telomere length and senescent-cell proportions in selected peripheral blood mononuclear cell subtypes

What the covered evidence found

The hyperbaric study enrolled 35 healthy adults age 64 or older and 30 completed the single-arm pre/post program. · Telomere analyses used 25 participants and senescent-cell analyses used 20, smaller subsets than the 30 completers. · The report described changes in telomere length and senescent-cell proportions in selected peripheral-blood immune-cell subtypes, not a clinical aging, healthspan or lifespan endpoint. · Without a comparison group, the study cannot separate the program from time, measurement variation, regression to the mean or other explanations, and multiple cell types and time points increase interpretive uncertainty. · Several authors worked for AVIV Scientific and one author was an AVIV shareholder, a material commercial conflict that should accompany interpretation.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to the named study design, population, exposure and measured endpoint; it must not be generalized into proof of disease prevention, rejuvenation, healthspan improvement or longer life.

Funding and conflicts: The hyperbaric study states that several authors worked for AVIV Scientific and that one author was an AVIV shareholder; the article therefore treats the single-arm biomarker findings as hypothesis-generating rather than independent efficacy evidence.

Correction/retraction state: none

Connected reporting

Hyperbaric oxygen changed selected blood-cell markers—not aging itself

Measured outcome: selected blood-cell telomere and senescence markers

Released conclusion: A small uncontrolled study reported telomere and senescent-cell changes in selected blood-cell subtypes. It did not test clinical aging, healthspan or lifespan, and commercial conflicts matter.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from fourteenth-coverage-edition.json

peer-reviewed · peer-reviewed

Pearl Results

DOI 10.18632/aging.206235

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed
Study designOther human evidencestudy publication
Population or modelPeopleMaturity described in linked reporting
Population/model
humans
Intervention and comparator
rapamycin; small randomized trial
Duration
Not separately structured in this publication record
Measured outcome
visceral fat, body composition, biomarkers, surveys and safety

What the covered evidence found

The 48-week randomized trial reported a null primary outcome, exploratory signals and substantial limits on broader healthy-aging claims.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: See the linked story for study-specific limitations and applicability boundaries.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: not separately structured

Connected reporting

PEARL trial found no change in its main visceral-fat outcome

Measured outcome: visceral fat, body composition, biomarkers, surveys and safety

Released conclusion: The 48-week randomized trial reported a null primary outcome, exploratory signals and substantial limits on broader healthy-aging claims.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT04488601

Identifier and correction state checked · projected from first-coverage-pilot.json

secondary-safety-analysis · peer-reviewed

ACCORD hypoglycemia and mortality analysis

PMID 20061358

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedsecondary-safety-analysis
Study designOther human evidencesecondary safety analysis
Population or modelPeopleLarge randomized cardiovascular-outcome trial with an early-stopped intensive glycemia arm
Population/model
ACCORD cohort with independent ADVANCE countercontext
Intervention and comparator
Different intensive and standard glucose-control strategies
Duration
Active trial and later analyses
Measured outcome
Safety and applicability

What the covered evidence found

Assistance-requiring hypoglycemia and weight gain over 10 kg were more frequent; hypoglycemia did not explain the mortality difference and a different intensive strategy in ADVANCE did not increase mortality.

What it does not establish

No single causal mechanism or cross-trial efficacy ranking

Limitations: Mechanism remains unresolved and trials differ materially

Funding and conflicts: NHLBI/NIH/CDC support; manufacturers supplied medicines/equipment and multiple author industry relationships were disclosed.

Correction/retraction state: none-linked-as-of-2026-08-26

Connected reporting

ACCORD’s intensive glucose target increased mortality and was stopped early

Measured outcome: major cardiovascular events, all-cause mortality and treatment harms

Released conclusion: The primary cardiovascular outcome was not significantly lower (352 versus 371 events; hazard ratio 0.90; P=0.16). Deaths were higher with intensive treatment (257 versus 203; hazard ratio 1.22; P=0.04), prompting early discontinuation.

Boundary: ACCORD does not show that all glucose lowering is harmful; it tested one intensive, multi-drug target strategy in a high-risk population.

Applicable registry records: NCT00000620

Identifier and correction state checked · projected from seventeenth-coverage-claim-map.json

peer-reviewed-secondary-analysis · peer-reviewed

Ttrials Walking Secondary

PMID 30366567

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-secondary-analysis
Study designOther human evidenceprespecified secondary analysis
Population or modelPeoplehuman randomized evidence for domain-specific function outcomes, with no direct disability, healthspan, mortality, or lifespan endpoint
Population/model
Testosterone Trials participants with and without enrollment in the Physical Function Trial
Intervention and comparator
testosterone; one-year randomized trials
Duration
Not separately structured in this publication record
Measured outcome
Six-minute walk distance, self-reported walking ability, and falls

What the covered evidence found

Across all participants, the mean between-group six-minute walk-distance difference was 6.69 meters; secondary analyses describe the mobility effect as modest and found no difference in falls. · The one-year Testosterone Trials do not establish frailty reversal, disability prevention, dementia prevention, healthspan extension, or lifespan extension, and were too small for broad long-term safety conclusions.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Applies to selected symptomatic men age 65 or older with repeated low testosterone treated with monitored 1% gel for one year; modest functional results do not establish disability prevention or anti-aging efficacy.

Funding and conflicts: The Testosterone Trials were principally publicly supported, with study product and additional support disclosed by investigators; the trials were not large or long enough for broad safety conclusions.

Correction/retraction state: none

Connected reporting

Testosterone’s walking result was modest—not an anti-aging effect

Measured outcome: six-minute walking distance and a 50-meter improvement threshold

Released conclusion: The prespecified Physical Function Trial threshold was not significant in its enrolled subgroup; broader secondary walking results do not establish disability prevention, healthspan or longevity.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00799617

Identifier and correction state checked · projected from twelfth-coverage-edition.json

primary-final-report · peer-reviewed

STRIDE PCORI final report

PMID 39869722

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-final-report
Study designOther human evidenceprimary final report
Population or modelPeopleLarge pragmatic cluster-randomized trial with a nonsignificant primary serious-injury result
Population/model
STRIDE selected primary-care population and measured fall outcomes
Intervention and comparator
nurse-led multifactorial fall-injury prevention; pragmatic cluster-randomized trial across 86 primary-care practices; enhanced usual care with falls-prevention information
Duration
Not separately structured in this publication record
Measured outcome
time to first adjudicated serious fall injury

What the covered evidence found

5,451 higher-risk primary-care patients; nurse-led multifactorial strategy versus enhanced usual care · 4.9 versus 5.3 serious injuries per 100 person-years; HR 0.92, P=.25 · First self-reported injury HR 0.90 · Hospitalizations and deaths were similar; representativeness and fidelity limits remain

What it does not establish

Every multifactorial service · Significant primary reduction or equivalence · Replacement of the primary adjudicated result · Independence or lifespan benefit

Limitations: Cluster pragmatic delivery · Confidence interval includes benefit and no difference · Secondary and self-reported · Incomplete process measures

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none-linked-as-of-2026-08-26

Connected reporting

STRIDE did not significantly reduce serious fall injuries in primary care

Measured outcome: time to first adjudicated serious fall injury

Released conclusion: First serious fall-injury rates were 4.9 versus 5.3 per 100 person-years; HR 0.92 (95% CI 0.80–1.06), P=.25.

Boundary: The trial did not establish a significant primary-outcome reduction, equivalence, longer independence, healthspan or lifespan.

Applicable registry records: NCT02475850

Identifier and correction state checked · projected from eighteenth-coverage-claim-map.json

peer-reviewed-safety · peer-reviewed

Select Safety

PMID 39948761

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-safety
Study designOther human evidencesafety analysis
Population or modelPeoplerandomized disease-outcome evidence and approved population-specific cardiovascular indication
Population/model
SELECT trial population
Intervention and comparator
GLP-1 drugs; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
adverse events and discontinuation

What the covered evidence found

Discontinuation and gastrointestinal adverse-event tradeoffs remained material in SELECT.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Trial and current regulatory data do not predict an individual's risk; FDA's January 2026 class review found no increased suicidal-behavior or ideation risk, while other label warnings remain.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Semaglutide reduced cardiovascular events in SELECT—not aging

Measured outcome: major cardiovascular events and safety

Released conclusion: The randomized result and approved indication are population-specific; anti-aging, healthspan and lifespan claims were not tested.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03574597

Identifier and correction state checked · projected from fourth-coverage-edition.json

public-health-guidance · publication record

Cdc Flu Guidance 2025 26

Source cdc-flu-acip-2025-26

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepublication recordpublic-health-guidance
Study designOther human evidencepublic health guidance
Population or modelPeoplelarge randomized influenza-illness evidence plus current product-category public-health guidance
Population/model
adults age 65 or older receiving influenza vaccination in the 2025–2026 U.S. season
Intervention and comparator
influenza vaccine; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
preferential product categories and the fallback when a preferred product is unavailable

What the covered evidence found

For adults age 65 or older, current CDC guidance preferentially recommends high-dose inactivated, recombinant or adjuvanted influenza vaccine; if none is available, any age-appropriate influenza vaccine should be used.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This is dated public-health guidance, not a head-to-head finding that one preferred product is universally best or personalized advice for an individual.

Funding and conflicts: Sanofi funded the high-dose trial and had primary responsibility for design, monitoring, data collection, analysis and statistics.

Correction/retraction state: none

Connected reporting

High-dose flu vaccine reduced influenza—not immune aging

Measured outcome: laboratory-confirmed influenza, immunogenicity and safety

Released conclusion: The randomized result was 1.4% versus 1.9% influenza across two seasons, not proof of immune rejuvenation or longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01427309

Identifier and correction state checked · projected from tenth-coverage-edition.json

public-health-guidance · publication record

Cdc Rsv Guidance 2026

Source cdc-rsv-adults-2026-02-24

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepublication recordpublic-health-guidance
Study designOther human evidencepublic health guidance
Population or modelPeoplethree large randomized product-specific trials plus maturing durability and postauthorization safety evidence
Population/model
U.S. adults age 75 or older and adults age 50–74 at increased risk of severe RSV disease
Intervention and comparator
RSV vaccines; three randomized vaccine trials
Duration
Not separately structured in this publication record
Measured outcome
current one-dose recommendation, product-neutral guidance, timing and repeat-dose uncertainty

What the covered evidence found

CDC guidance dated February 24, 2026 recommends one RSV vaccine dose for all adults age 75 or older and adults age 50–74 at increased risk; it expresses no product preference and does not currently recommend annual or repeat dosing. · Separate Arexvy, Abrysvo and mResvia trials do not establish a head-to-head product ranking because case definitions, populations, follow-up and analysis times differ.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Guidance can change and is not a personalized product or timing recommendation; individual eligibility and contraindications require current clinical context. · Cross-trial percentages are descriptive only; CDC currently expresses no product preference.

Funding and conflicts: The Arexvy, Abrysvo and mResvia pivotal trials were funded by GSK, Pfizer and Moderna, respectively; current guidance and postauthorization safety context come from CDC and FDA.

Correction/retraction state: none

Connected reporting

RSV vaccines reduce respiratory disease. Separate trials cannot rank them

Measured outcome: RSV lower-respiratory disease or illness, acute respiratory disease and safety

Released conclusion: Arexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT04886596 · NCT05035212 · NCT05127434

Identifier and correction state checked · projected from tenth-coverage-edition.json

regulatory-guidance · publication record

Fda Aspirin Safety

Source fda-aspirin-facts-2026

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepublication recordregulatory-guidance
Study designOther human evidenceregulatory safety guidance
Population or modelPeoplelarge human randomized primary-prevention evidence over median 4.7 years · large human randomized evidence for prespecified cardiovascular and bleeding outcomes · randomized-period secondary mortality evidence plus trial-derived observational extension follow-up
Population/model
Consumers considering aspirin for preventive use
Intervention and comparator
low-dose aspirin; large randomized trial · low-dose aspirin; large randomized trial · low-dose aspirin; randomized trial plus observational extension
Duration
Not separately structured in this publication record
Measured outcome
Bleeding, interaction and clinician-guidance context

What the covered evidence found

ASPREE studied primary prevention; its findings do not erase aspirin's established uses for selected people with cardiovascular disease or prior events. · FDA says daily preventive aspirin is not right for everyone, can cause serious bleeding, and should be considered with a health professional rather than self-directed.

What it does not establish

ASPREE found no gain in disability-free survival—and more major bleeding · ASPREE did not lower cardiovascular events—and increased major bleeding · ASPREE’s cancer signal changed across longer follow-up

Limitations: Applies to ASPREE's selected primary-prevention population, 100 mg daily enteric-coated aspirin versus placebo, median 4.7 years randomized follow-up and incomplete late adherence; it does not determine secondary-prevention benefit or an individual medication decision. · FDA safety information is general regulatory guidance; it does not individualize indication, dose, bleeding risk, drug interactions, secondary-prevention needs, or whether a particular person should start, continue, or stop aspirin.

Funding and conflicts: ASPREE was supported by US and Australian public/institutional funders; Bayer supplied aspirin and matching placebo in kind and was reported to have no other trial role. The 2026 follow-up discloses author grants and several outside pharmaceutical relationships.

Correction/retraction state: not-applicable

Connected reporting

ASPREE found no gain in disability-free survival—and more major bleeding

Measured outcome: disability-free survival · major bleeding

Released conclusion: In 19,114 selected older adults, daily low-dose aspirin did not improve the trial’s composite of death, dementia or persistent physical disability over a median 4.7 years. Major hemorrhage was higher.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

ASPREE did not lower cardiovascular events—and increased major bleeding

Measured outcome: cardiovascular events · major bleeding

Released conclusion: In selected older adults without cardiovascular disease, low-dose aspirin did not significantly reduce the trial’s cardiovascular composite. Major hemorrhage occurred more often.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

ASPREE’s cancer signal changed across longer follow-up

Measured outcome: cancer mortality · long-term follow-up

Released conclusion: The randomized trial found an unexpected cancer-mortality imbalance. Longer follow-up found no difference in overall cancer incidence and no post-trial mortality legacy effect.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01038583

Identifier and correction state checked · projected from thirteenth-coverage-edition.json

regulator-label · publication record

Fda Shingrix Label

Source fda-shingrix-2026

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepublication recordregulator-label
Study designOther human evidenceregulator label review
Population or modelPeoplestrong randomized shingles-prevention evidence with emerging observational and quasi-experimental dementia evidence
Population/model
people within current U.S. Shingrix labeled indications
Intervention and comparator
shingles vaccine; randomized and non-randomized evidence
Duration
Not separately structured in this publication record
Measured outcome
approved prevention indication and labeled population, excluding dementia prevention

What the covered evidence found

Current evidence does not establish recombinant zoster vaccination as a causal dementia-prevention treatment or an FDA-approved dementia indication.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The dementia studies are observational or quasi-experimental and involve different vaccine formulations; a randomized dementia endpoint has not been established.

Funding and conflicts: GSK funded ZOE-50. The recombinant-dementia EHR study had NIHR/Wellcome/JDRF support and disclosed one author's GSK consultancy and Oxford–GSK role; GSK was reported uninvolved. The Welsh study reported public and philanthropic grants and no competing interests.

Correction/retraction state: none

Connected reporting

Shingles vaccines prevent shingles. Dementia evidence remains non-randomized

Measured outcome: herpes-zoster disease and recorded dementia diagnoses

Released conclusion: Randomized trials established shingles prevention. Dementia findings come from observational and quasi-experimental studies and do not prove prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01165177

Identifier and correction state checked · projected from tenth-coverage-edition.json

regulator · publication record

Fda Traverse Label Review

Source fda-testosterone-labeling-2025

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepublication recordregulator
Study designOther human evidenceregulatory evidence review
Population or modelMixed or synthesislarge human randomized noninferiority evidence for one cardiovascular composite, with limited duration and separate safety signals
Population/model
FDA class-wide review of testosterone products using TRAVERSE and postmarket ambulatory blood-pressure studies
Intervention and comparator
testosterone; large randomized noninferiority trial
Duration
Not separately structured in this publication record
Measured outcome
Cardiovascular boxed-warning language and class-wide blood-pressure warnings

What the covered evidence found

On February 28, 2025, FDA said TRAVERSE supported removing cardiovascular-risk language from the boxed warning while ambulatory blood-pressure studies supported class-wide blood-pressure warnings; that notice retained the age-related-hypogonadism limitation at that time.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Regulatory language is dated, product-specific prescribing information may differ, and a label revision is neither a treatment recommendation nor evidence of longevity benefit.

Funding and conflicts: TRAVERSE was an FDA-required postmarketing trial funded by an industry consortium led by AbbVie; sponsor and investigator roles require visible disclosure.

Correction/retraction state: none

Connected reporting

TRAVERSE found cardiovascular noninferiority—not a longevity benefit

Measured outcome: major cardiovascular events and cardiovascular safety outcomes

Released conclusion: Among selected men with hypogonadism and elevated cardiovascular risk, testosterone gel was noninferior to placebo for major cardiovascular events; the trial did not test longer life or general anti-aging use.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03518034

Identifier and correction state checked · projected from twelfth-coverage-edition.json

regulator · publication record

Fda 2026 Label Review

Source hhs-testosterone-labels-2026

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepublication recordregulator
Study designOther human evidenceregulatory evidence review
Population or modelPeoplelarge human randomized noninferiority evidence for one cardiovascular composite, with limited duration and separate safety signals
Population/model
FDA and HHS review of testosterone-replacement-therapy prescribing information
Intervention and comparator
testosterone; large randomized noninferiority trial
Duration
Not separately structured in this publication record
Measured outcome
Requested limitation-of-use, prostate-cancer, and benign-prostatic-hyperplasia label revisions

What the covered evidence found

On June 18, 2026, HHS announced FDA-requested removal of the age-related-hypogonadism limitation-of-use language and revisions to prostate-cancer and benign-prostatic-hyperplasia information.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Regulatory language is dated, product-specific prescribing information may differ, and a label revision is neither a treatment recommendation nor evidence of longevity benefit.

Funding and conflicts: TRAVERSE was an FDA-required postmarketing trial funded by an industry consortium led by AbbVie; sponsor and investigator roles require visible disclosure.

Correction/retraction state: none

Connected reporting

TRAVERSE found cardiovascular noninferiority—not a longevity benefit

Measured outcome: major cardiovascular events and cardiovascular safety outcomes

Released conclusion: Among selected men with hypogonadism and elevated cardiovascular risk, testosterone gel was noninferior to placebo for major cardiovascular events; the trial did not test longer life or general anti-aging use.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03518034

Identifier and correction state checked · projected from twelfth-coverage-edition.json

clinical-guidance · publication record

Uspstf Aspirin Guidance

Source uspstf-aspirin-2022

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepublication recordclinical-guidance
Study designOther human evidenceevidence guidance review
Population or modelPeoplelarge human randomized primary-prevention evidence over median 4.7 years · large human randomized evidence for prespecified cardiovascular and bleeding outcomes
Population/model
Adults without known cardiovascular disease considered for primary prevention
Intervention and comparator
low-dose aspirin; large randomized trial · low-dose aspirin; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
Dated initiation recommendation by age

What the covered evidence found

The April 26, 2022 USPSTF recommendation advises against initiating low-dose aspirin for primary CVD prevention in adults 60 or older.

What it does not establish

ASPREE found no gain in disability-free survival—and more major bleeding · ASPREE did not lower cardiovascular events—and increased major bleeding

Limitations: Applies to ASPREE's selected primary-prevention population, 100 mg daily enteric-coated aspirin versus placebo, median 4.7 years randomized follow-up and incomplete late adherence; it does not determine secondary-prevention benefit or an individual medication decision.

Funding and conflicts: ASPREE was supported by US and Australian public/institutional funders; Bayer supplied aspirin and matching placebo in kind and was reported to have no other trial role. The 2026 follow-up discloses author grants and several outside pharmaceutical relationships.

Correction/retraction state: not-applicable

Connected reporting

ASPREE found no gain in disability-free survival—and more major bleeding

Measured outcome: disability-free survival · major bleeding

Released conclusion: In 19,114 selected older adults, daily low-dose aspirin did not improve the trial’s composite of death, dementia or persistent physical disability over a median 4.7 years. Major hemorrhage was higher.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

ASPREE did not lower cardiovascular events—and increased major bleeding

Measured outcome: cardiovascular events · major bleeding

Released conclusion: In selected older adults without cardiovascular disease, low-dose aspirin did not significantly reduce the trial’s cardiovascular composite. Major hemorrhage occurred more often.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01038583

Identifier and correction state checked · projected from thirteenth-coverage-edition.json

Randomized trial

85 covered publications

peer-reviewed-primary · peer-reviewed

Whi Combined Primary

DOI 10.1001/jama.288.3.321

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplerandomized human chronic-disease evidence plus long-term mortality and regimen-specific breast-cancer follow-up
Population/model
16,608 postmenopausal women age 50–79 with a uterus
Intervention and comparator
menopausal hormone therapy; randomized trials
Duration
Not separately structured in this publication record
Measured outcome
chronic-disease, cancer, thromboembolism and fracture outcomes over mean 5.2 years

What the covered evidence found

In 16,608 postmenopausal women age 50–79 with a uterus, CEE plus MPA over a mean 5.2 years increased coronary-heart-disease, stroke, pulmonary-embolism and invasive-breast-cancer events while reducing colorectal-cancer and hip-fracture events. · Approximate attributable differences per 10,000 person-years for CEE plus MPA were 7 more coronary events, 8 more strokes, 8 more pulmonary emboli and 8 more invasive breast cancers, with 6 fewer colorectal cancers and 5 fewer hip fractures. · WHI tested chronic-disease prevention rather than symptom relief; current synthesis recognizes an individualized symptom-treatment role while not supporting hormone therapy for general chronic-disease or longevity prevention.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The balance is specific to the tested combined regimen and cannot be generalized to estrogen alone or every hormone formulation. · Trial-level absolute differences are not individualized risk predictions and combine distinct outcomes that must remain separately labeled. · Clinical context does not provide individualized treatment advice and does not turn a symptom indication into a prevention claim.

Funding and conflicts: NIH/NHLBI sponsored the WHI hormone trials; Wyeth-Ayerst donated study drugs. Regimen-specific disclosures remain visible.

Correction/retraction state: none

Connected reporting

Menopausal hormone therapy treats symptoms. WHI did not show a longevity benefit

Measured outcome: disease events, breast cancer and all-cause mortality

Released conclusion: WHI found a formulation-specific mix of benefits and harms, no overall 18-year mortality difference, and no basis for general longevity prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00000611

Identifier and correction state checked · projected from ninth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Active Original

DOI 10.1001/jama.288.18.2271

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplerandomized trained-ability evidence plus long-term function, mortality and contested claims-based dementia analyses
Population/model
2,832 independent adults age 65–94 in six US metropolitan areas
Intervention and comparator
cognitive training; randomized trial plus disputed secondary analysis
Duration
Not separately structured in this publication record
Measured outcome
trained memory, reasoning and speed-of-processing abilities

What the covered evidence found

ACTIVE memory, reasoning and speed training improved specifically trained abilities; ten-year persistence was detectable for reasoning and speed, not memory. · The studied adaptive dual-attention speed protocol does not establish benefit from generic brain games or every commercial implementation.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Performance on trained domains is not proof of generalized cognitive rejuvenation. · Protocol-specific trial evidence cannot be transferred to untested products or games.

Funding and conflicts: NIH-supported trial and follow-ups; the 20-year mortality report declared no conflicts, while commercial descendants are not evidence for the studied protocol.

Correction/retraction state: none

Connected reporting

Cognitive training improved practiced skills—not survival or proven dementia prevention

Measured outcome: trained abilities, daily function, all-cause mortality and claims-diagnosed dementia

Released conclusion: ACTIVE supports trained-ability gains and some function signals, found no mortality benefit, and leaves a claims-based dementia subgroup methodologically disputed.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00298558

Identifier and correction state checked · projected from eighth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Cbti Zopiclone Placebo

DOI 10.1001/jama.295.24.2851

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplehuman randomized evidence for sleep outcomes, with no direct longevity or dementia endpoint
Population/model
46 adults with chronic primary insomnia, mean age 60.8 years
Intervention and comparator
CBT-I; randomized behavioral trials
Duration
Not separately structured in this publication record
Measured outcome
polysomnographic and diary sleep outcomes over six weeks and follow-up

What the covered evidence found

In a 46-person trial of older adults with chronic primary insomnia, CBT-I improved several objective sleep outcomes and was more durable than zopiclone or placebo for the studied sleep endpoints. · The featured CBT-I trials measured sleep outcomes, not biological aging, dementia incidence, mortality, healthspan or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The trial was small, enrolled a defined primary-insomnia population and did not test dementia, mortality, biological aging, healthspan or lifespan. · Absence of a longevity endpoint cannot be converted into evidence for or against lifespan extension.

Funding and conflicts: The featured CBT-I trials reported public or academic support; the evidence does not establish dementia prevention or longer life.

Correction/retraction state: none

Connected reporting

CBT-I improves later-life insomnia—not aging itself

Measured outcome: sleep latency, sleep efficiency, insomnia remission and durability

Released conclusion: Two randomized trials support meaningful sleep improvement in older adults; they did not test dementia prevention, biological aging or lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00280020 · NCT00295386

Identifier and correction state checked · projected from eleventh-coverage-edition.json

peer-reviewed-primary · peer-reviewed

LIFE mobility trial

DOI 10.1001/jama.2014.5616

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplerandomized human evidence for specific functional outcomes; lifespan evidence unavailable
Population/model
1,635 adults aged 70–89
Intervention and comparator
exercise; randomized trials
Duration
Not separately structured in this publication record
Measured outcome
major mobility disability

What the covered evidence found

The LIFE program reduced major mobility disability in its enrolled older population. · The featured physical-activity trials do not establish lifespan extension.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Population could walk 400 m at baseline; no significant mortality or hospitalization benefit. · Lifespan was not demonstrated by either program.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Structured physical activity reduced late-life mobility disability—not aging itself

Measured outcome: mobility disability and discharge function

Released conclusion: LIFE supports a meaningful mobility outcome in vulnerable older adults, while lifespan and universal-program claims remain untested.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Exercise has strong evidence for function—not proof of slower biological aging

Measured outcome: mobility, function, frailty, falls and all-cause mortality

Released conclusion: Human trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01072500 · NCT02300896

Identifier and correction state checked · projected from fourth-coverage-edition.json

peer-reviewed-follow-up · peer-reviewed

Whi Pooled Mortality

DOI 10.1001/jama.2017.11217

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-follow-up
Study designRandomized trialrandomized trial follow up
Population or modelPeoplerandomized human chronic-disease evidence plus long-term mortality and regimen-specific breast-cancer follow-up
Population/model
27,347 women randomized in the two WHI hormone-therapy trials
Intervention and comparator
menopausal hormone therapy; randomized trials
Duration
Not separately structured in this publication record
Measured outcome
all-cause and cause-specific mortality through 18 years

What the covered evidence found

Across both randomized WHI hormone trials, 18-year all-cause mortality was 27.1% with hormone therapy versus 27.6% with placebo (HR 0.99, 95% CI 0.94–1.03). · The WHI evidence does not establish that menopausal hormone therapy extends human lifespan or reverses aging.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Pooled long-term follow-up after limited-duration randomization establishes neither a longevity benefit nor an overall mortality penalty. · A null overall mortality comparison is not evidence of lifespan extension or biological rejuvenation.

Funding and conflicts: NIH/NHLBI sponsored the WHI hormone trials; Wyeth-Ayerst donated study drugs. Regimen-specific disclosures remain visible.

Correction/retraction state: none

Connected reporting

Menopausal hormone therapy treats symptoms. WHI did not show a longevity benefit

Measured outcome: disease events, breast cancer and all-cause mortality

Released conclusion: WHI found a formulation-specific mix of benefits and harms, no overall 18-year mortality difference, and no basis for general longevity prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00000611

Identifier and correction state checked · projected from ninth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Sprint Mind

DOI 10.1001/jama.2018.21442

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial secondary analysis
Population or modelPeoplelarge randomized human cardiovascular-outcomes evidence with secondary and post-trial cognitive follow-up
Population/model
SPRINT participants with adjudicated cognitive follow-up
Intervention and comparator
blood pressure; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
probable dementia and mild cognitive impairment

What the covered evidence found

SPRINT MIND did not significantly reduce probable dementia; its favorable mild-cognitive-impairment result was secondary and SPRINT did not test biological aging or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The later cognitive report followed participants observationally after the randomized treatment period.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

SPRINT reduced cardiovascular events—not aging itself

Measured outcome: cardiovascular events, mortality, adverse events and cognitive outcomes

Released conclusion: Intensive treatment lowered cardiovascular events and mortality in eligible high-risk adults, with more hypotension, electrolyte problems and kidney injury.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01206062

Identifier and correction state checked · projected from sixth-coverage-edition.json

peer-reviewed-follow-up · peer-reviewed

Whi Breast Follow Up

DOI 10.1001/jama.2020.9482

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-follow-up
Study designRandomized trialrandomized trial follow up
Population or modelAnimal modelrandomized human chronic-disease evidence plus long-term mortality and regimen-specific breast-cancer follow-up
Population/model
women in the two WHI hormone trials, separated by regimen and uterus status
Intervention and comparator
menopausal hormone therapy; randomized trials
Duration
Not separately structured in this publication record
Measured outcome
long-term breast-cancer incidence and mortality

What the covered evidence found

Long-term breast outcomes differed between CEE alone after hysterectomy and CEE plus MPA in women with a uterus.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The regimen-specific incidence and mortality estimates cannot be transferred across formulations or uterus status.

Funding and conflicts: NIH/NHLBI sponsored the WHI hormone trials; Wyeth-Ayerst donated study drugs. Regimen-specific disclosures remain visible.

Correction/retraction state: none

Connected reporting

Menopausal hormone therapy treats symptoms. WHI did not show a longevity benefit

Measured outcome: disease events, breast cancer and all-cause mortality

Released conclusion: WHI found a formulation-specific mix of benefits and harms, no overall 18-year mortality difference, and no basis for general longevity prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00000611

Identifier and correction state checked · projected from ninth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Ttrials Bone

DOI 10.1001/jamainternmed.2016.9539

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial substudy
Population or modelPeoplelarge randomized clinical-fracture evidence contrasted with an earlier small one-year bone-density surrogate substudy
Population/model
211 men age 65 or older with two low testosterone measurements in the Testosterone Trials
Intervention and comparator
testosterone; randomized trials
Duration
Not separately structured in this publication record
Measured outcome
One-year volumetric bone mineral density and estimated bone strength

What the covered evidence found

In a 211-person Testosterone Trials substudy, one year of testosterone increased spine trabecular volumetric BMD 7.5% versus 0.8% with placebo, a 6.8-percentage-point treatment effect, and increased estimated spine strength. · An improvement in bone-density or estimated-strength surrogates cannot be substituted for the later randomized clinical-fracture outcome.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: One-year volumetric BMD and estimated strength are surrogate measurements in a small substudy; they are not clinical fractures and cannot establish disability, healthspan, or lifespan benefit.

Funding and conflicts: TRAVERSE was an FDA-required postmarketing trial funded by an industry consortium led by AbbVie; sponsor and investigator roles require visible disclosure. The Testosterone Trials were principally publicly supported, with study product and additional support disclosed by investigators; the trials were not large or long enough for broad safety conclusions.

Correction/retraction state: none

Connected reporting

Testosterone did not prevent fractures in TRAVERSE

Measured outcome: clinical fractures and bone-density measures

Released conclusion: Clinical fractures were more frequent with testosterone than placebo in TRAVERSE; a smaller substudy’s bone-density gain cannot substitute for fracture outcomes.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00799617 · NCT03518034

Identifier and correction state checked · projected from twelfth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Hospital Multicomponent

DOI 10.1001/jamainternmed.2018.4869

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplerandomized human evidence for specific functional outcomes; lifespan evidence unavailable
Population/model
370 hospitalized adults, mean age 87.3
Intervention and comparator
exercise; randomized trials
Duration
Not separately structured in this publication record
Measured outcome
discharge function

What the covered evidence found

A brief supervised inpatient program improved discharge function in one very-old population. · The featured physical-activity trials do not establish lifespan extension.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Single center, median five days, no three-month mortality or readmission benefit. · Lifespan was not demonstrated by either program.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Structured physical activity reduced late-life mobility disability—not aging itself

Measured outcome: mobility disability and discharge function

Released conclusion: LIFE supports a meaningful mobility outcome in vulnerable older adults, while lifespan and universal-program claims remain untested.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01072500 · NCT02300896

Identifier and correction state checked · projected from fourth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Treat

DOI 10.1001/jamainternmed.2020.4153

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeopleshort randomized human evidence
Population/model
116 adults with overweight or obesity
Intervention and comparator
meal timing; short randomized trials
Duration
Not separately structured in this publication record
Measured outcome
12-week weight and metabolic outcomes

What the covered evidence found

TREAT found no significant 12-week between-group weight benefit from a noon-to-8 p.m. eating window. · These time-restricted-eating trials did not test biological aging, healthspan, mortality or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Short duration; corrected publication; in-person body-composition subset was smaller. · Absence of a measured endpoint cannot be converted into benefit or harm.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: corrected

Connected reporting

Human time-restricted-eating trials show mixed short-term results—not slower aging

Measured outcome: weight, body composition, visceral fat and cardiometabolic markers

Released conclusion: Different eating windows and comparators produced different weight and fat findings; none tested biological aging, healthspan or lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03393195 · NCT03459703 · NCT05310721

Identifier and correction state checked · projected from fifth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Early Tre

DOI 10.1001/jamainternmed.2022.3050

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeopleshort randomized human evidence
Population/model
90 adults with obesity
Intervention and comparator
meal timing; short randomized trials
Duration
Not separately structured in this publication record
Measured outcome
14-week weight, fat and cardiometabolic outcomes

What the covered evidence found

Other short trials reported comparator-specific weight or blood-pressure signals but no consistent visceral-fat benefit. · These time-restricted-eating trials did not test biological aging, healthspan, mortality or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Timing, counseling, energy restriction, populations and endpoints differed. · Absence of a measured endpoint cannot be converted into benefit or harm.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Human time-restricted-eating trials show mixed short-term results—not slower aging

Measured outcome: weight, body composition, visceral fat and cardiometabolic markers

Released conclusion: Different eating windows and comparators produced different weight and fat findings; none tested biological aging, healthspan or lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03393195 · NCT03459703 · NCT05310721

Identifier and correction state checked · projected from fifth-coverage-edition.json

peer-reviewed-primary-randomized-trial · peer-reviewed

Energize Urolithin A

DOI 10.1001/jamanetworkopen.2021.44279

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-randomized-trial
Study designRandomized trialdouble blind placebo controlled randomized trial
Population or modelPeoplesmall four-month randomized human trial with two null primary outcomes and secondary muscle-endurance and biomarker signals
Population/model
66 selected adults age 65 to 90 with lower mitochondrial function at two Seattle sites
Intervention and comparator
urolithin A; small randomized trial
Duration
Not separately structured in this publication record
Measured outcome
Four-month six-minute walk and ATP-production primary outcomes plus endurance and biomarker secondary outcomes

What the covered evidence found

ENERGIZE randomized 66 selected adults age 65 to 90 with lower mitochondrial function, 33 per arm; mean age was 71.7, 75.8% were women and all participants identified as White. · After four months, 1,000 mg/day urolithin A did not significantly improve either co-primary comparison: six-minute walk distance or maximal ATP production in hand skeletal muscle versus placebo. · Mean six-minute walk distance increased 60.8 m with urolithin A and 42.5 m with placebo, but the between-group primary comparison was not significant. · Hand and leg muscle endurance improved versus placebo at two months, while selected acylcarnitines, ceramides and C-reactive protein changed at four months; these were secondary outcomes. · Adverse-event counts did not differ statistically and no serious adverse events were reported over four months, but ENERGIZE did not establish long-term safety, disability prevention, healthspan or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to a small, short trial in selected older adults from two Seattle sites using one 1,000 mg branded formulation; it cannot establish disability prevention, long-term safety, healthspan or lifespan.

Funding and conflicts: The publication disclosed Amazentis employees, its founder and chief executive, board leadership, company shareholdings, and patent interests. That direct sponsor and intellectual-property involvement must remain visible alongside the short duration and selected study population.

Correction/retraction state: none

Connected reporting

Urolithin A missed both primary outcomes in older adults

Measured outcome: walking distance, muscle endurance and ATP production

Released conclusion: ENERGIZE found no significant benefit for six-minute walk distance or maximal ATP production. Secondary endurance and biomarker signals remain preliminary and do not establish disability prevention or longer healthy life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03283462

Identifier and correction state checked · projected from fifteenth-coverage-edition.json

peer-reviewed-primary-randomized-trial · peer-reviewed

Smartage Phase 2b

DOI 10.1001/jamanetworkopen.2022.13875

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-randomized-trial
Study designRandomized trialsingle center double masked placebo controlled randomized trial
Population or modelPeoplephase 2b randomized human cognitive-outcome evidence with a null primary result and only exploratory verbal-memory and inflammation signals
Population/model
100 adults age 60 to 90 with subjective cognitive decline
Intervention and comparator
wheat-germ spermidine extract; small randomized phase 2b trial
Duration
Not separately structured in this publication record
Measured outcome
Twelve-month mnemonic discrimination primary outcome plus prespecified secondary and exploratory outcomes

What the covered evidence found

SmartAge randomized 100 adults age 60 to 90 with subjective cognitive decline to 0.9 mg/day of a wheat-germ-derived spermidine extract or microcrystalline-cellulose placebo for 12 months. · The intention-to-treat primary mnemonic-discrimination result was null: between-group difference -0.03, 95% CI -0.11 to 0.05, P=.47. · Prespecified secondary outcomes were also null; verbal-memory and inflammation findings came from exploratory per-protocol or subgroup analyses and require validation. · Adverse events were balanced during 12 months, but that observation and the tested extract do not establish long-term safety or validate unrelated doses, formulations, combinations or retail products. · SmartAge did not test dementia incidence, disability, healthspan or lifespan and cannot support claims that spermidine prevents dementia or slows human aging.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to one single-center trial in selected older adults with subjective cognitive decline, one wheat-germ extract, one dose and twelve months; it cannot establish dementia prevention, broad cognitive benefit, healthspan or lifespan.

Funding and conflicts: German federal and academic support was disclosed. Several authors reported equity, executive or advisory roles, patents, or former equity involving Longevity Labs GmbH, which also supported development of the spermidine-rich extract; the paper states that funders had no role in trial conduct or reporting.

Correction/retraction state: none

Connected reporting

Spermidine did not improve the trial’s primary memory outcome

Measured outcome: memory and cognitive tests

Released conclusion: In the 12-month SmartAge trial, a wheat-germ spermidine extract did not improve the prespecified memory outcome or secondary outcomes. Exploratory signals do not establish dementia prevention or longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03094546

Identifier and correction state checked · projected from fifteenth-coverage-edition.json

peer-reviewed-follow-up · peer-reviewed

Aspree Xt Cancer

DOI 10.1001/jamaoncol.2025.6196

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-follow-up
Study designRandomized trialrandomized trial derived observational follow up
Population or modelPeoplerandomized-period secondary mortality evidence plus trial-derived observational extension follow-up
Population/model
19,114 community-dwelling older adults in Australia and the United States, generally age 70 or older (65 or older for Black and Hispanic US participants), without cardiovascular disease, dementia or independence-limiting physical disability at enrollment
Intervention and comparator
low-dose aspirin; randomized trial plus observational extension
Duration
Not separately structured in this publication record
Measured outcome
Cancer incidence and mortality across combined and post-trial follow-up

What the covered evidence found

ASPREE-XT was an observational extension after assigned aspirin or placebo stopped; post-trial legacy analyses are not continued randomized-treatment evidence. · Across median 8.6 years combined follow-up, original aspirin assignment was not associated with overall cancer incidence; HR 0.98, 95% CI 0.92 to 1.05. · Across combined follow-up, cancer-related mortality was higher by original aspirin assignment; HR 1.15, 95% CI 1.03 to 1.29. · In the post-trial legacy analysis, original aspirin assignment was not associated with cancer incidence; HR 0.91, 95% CI 0.82 to 1.01. · In the post-trial legacy analysis, original aspirin assignment was not associated with cancer mortality; HR 1.02, 95% CI 0.83 to 1.25.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Combined follow-up includes years after randomized study drug stopped; post-trial estimates compare original assignment but do not represent continued randomized exposure.

Funding and conflicts: ASPREE was supported by US and Australian public/institutional funders; Bayer supplied aspirin and matching placebo in kind and was reported to have no other trial role. The 2026 follow-up discloses author grants and several outside pharmaceutical relationships.

Correction/retraction state: none

Connected reporting

ASPREE’s cancer signal changed across longer follow-up

Measured outcome: cancer mortality · long-term follow-up

Released conclusion: The randomized trial found an unexpected cancer-mortality imbalance. Longer follow-up found no difference in overall cancer incidence and no post-trial mortality legacy effect.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01038583

Identifier and correction state checked · projected from thirteenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Cosmos Mind

DOI 10.1002/alz.12767

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial substudy
Population or modelPeoplemultiple correlated randomized substudies measuring cognitive-test performance and DNA-methylation biomarkers
Population/model
2,262 adults aged 65 and older
Intervention and comparator
multivitamins; correlated randomized substudies
Duration
Not separately structured in this publication record
Measured outcome
telephone cognitive-test composites over three years

What the covered evidence found

COSMOS cognitive substudies reported small improvements in some cognitive-test scores, with mixed results across domains. · The three cognitive reports are directionally consistent analyses from one parent COSMOS program rather than three independent replications.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Test-score differences do not establish dementia prevention or preserved independent function. · Shared recruitment and program infrastructure limit independence.

Funding and conflicts: NIH and other support; Pfizer Consumer Healthcare/Haleon supplied some pills and packaging.

Correction/retraction state: none

Connected reporting

Multivitamins moved some tests and aging clocks. What does that mean?

Measured outcome: cognitive-test scores, word recall and DNA-methylation biomarkers

Released conclusion: COSMOS found small cognitive-test differences and modest movement in two DNA-methylation clocks; neither establishes dementia prevention or longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03035201 · NCT04582617

Identifier and correction state checked · projected from seventh-coverage-edition.json

peer-reviewed-extension · peer-reviewed

Horizon Extension

DOI 10.1002/jbmr.1494

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-extension
Study designRandomized trialrandomized extension
Population or modelPeoplelarge randomized human fracture evidence plus outcome-specific duration and current regulator safety context
Population/model
women completing three years of HORIZON zoledronic-acid treatment
Intervention and comparator
zoledronic acid; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
fractures, BMD and safety after continuing to six years or stopping at three

What the covered evidence found

Continuing annual zoledronic acid through six years versus stopping after three reduced morphometric vertebral fractures (3.0% versus 6.2%; OR 0.51, 95% CI 0.26–0.95) but did not significantly change hip, nonvertebral, clinical vertebral or all-clinical fractures.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The extension supports an outcome-specific duration distinction and not a rule that longer treatment is always better.

Funding and conflicts: Novartis sponsored HORIZON, with company involvement and author relationships disclosed in the primary reports.

Correction/retraction state: none

Connected reporting

Zoledronic acid reduced fractures in osteoporosis—not aging itself

Measured outcome: vertebral, hip and nonvertebral fractures plus bone density

Released conclusion: HORIZON reduced vertebral and hip fractures in postmenopausal osteoporosis, with outcome-specific duration and safety limits—not evidence of slower aging.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00049829 · NCT00145327

Identifier and correction state checked · projected from ninth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Liftmor Primary

DOI 10.1002/jbmr.3284

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplesmall randomized human BMD and function evidence with bounded vertebral-safety follow-up and a published correction
Population/model
101 screened postmenopausal women with low bone mass, mean age 65
Intervention and comparator
LIFTMOR; small supervised randomized trial
Duration
Not separately structured in this publication record
Measured outcome
eight-month BMD, strength, function, adherence and reported adverse events

What the covered evidence found

LIFTMOR randomized 101 screened postmenopausal women with low bone mass, mean age 65, to eight months of twice-weekly supervised HiRIT or home-based low-intensity exercise. · Per-protocol lumbar-spine BMD changed plus 2.9% versus minus 1.2%, and femoral-neck BMD plus 0.3% versus minus 1.9% in LIFTMOR. · Measured strength and functional outcomes favored supervised HiRIT over the low-intensity control. · One minor lower-back spasm was reported, and no incident vertebral deterioration attributable to training appeared in the assessed sample. · LIFTMOR did not establish fewer fragility fractures, lower mortality, greater healthspan or longer lifespan. · The LIFTMOR erratum corrected table headings and the sign of calcium-intake change; it did not create or reverse a bone or fracture outcome. · Griffith University and The Bone Clinic affiliations and later commercial translation require disclosure; clinic marketing is not efficacy evidence.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The small selected sample, per-protocol emphasis and active comparator limit generalization. · These per-protocol BMD changes are biomarkers and do not establish fracture prevention. · Measured function remains separate from BMD, fracture incidence, mortality, healthspan and lifespan. · A small, screened and closely supervised study is insufficient to establish safety for unscreened or unsupervised populations. · The trial was too small and short to establish fracture prevention or longevity outcomes. · The correction must remain visible without implying that unaffected outcomes were reanalyzed or reversed. · Affiliations and translation context require disclosure but do not independently prove or disprove efficacy.

Funding and conflicts: Griffith University and The Bone Clinic affiliations and later commercial translation require visible context; marketing is not efficacy evidence.

Correction/retraction state: corrected

Connected reporting

LIFTMOR improved bone density in a small supervised trial—not fracture prevention

Measured outcome: bone density, strength and functional measures

Released conclusion: LIFTMOR found BMD and function gains in a small, screened, closely supervised trial—not fracture prevention or proof that unsupervised heavy training is safe.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from ninth-coverage-edition.json

peer-reviewed-follow-up · peer-reviewed

Liftmor Vertebral Safety

DOI 10.1007/s00198-018-04829-z

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-follow-up
Study designRandomized trialrandomized trial follow up
Population or modelPeoplesmall randomized human BMD and function evidence with bounded vertebral-safety follow-up and a published correction
Population/model
assessed LIFTMOR participants with vertebral morphology imaging
Intervention and comparator
LIFTMOR; small supervised randomized trial
Duration
Not separately structured in this publication record
Measured outcome
vertebral morphology and incident vertebral fracture during the supervised program

What the covered evidence found

One minor lower-back spasm was reported, and no incident vertebral deterioration attributable to training appeared in the assessed sample. · LIFTMOR did not establish fewer fragility fractures, lower mortality, greater healthspan or longer lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: A small, screened and closely supervised study is insufficient to establish safety for unscreened or unsupervised populations. · The trial was too small and short to establish fracture prevention or longevity outcomes.

Funding and conflicts: Griffith University and The Bone Clinic affiliations and later commercial translation require visible context; marketing is not efficacy evidence.

Correction/retraction state: none

Connected reporting

LIFTMOR improved bone density in a small supervised trial—not fracture prevention

Measured outcome: bone density, strength and functional measures

Released conclusion: LIFTMOR found BMD and function gains in a small, screened, closely supervised trial—not fracture prevention or proof that unsupervised heavy training is safe.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from ninth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Cosmos Web

DOI 10.1016/j.ajcnut.2023.05.011

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial substudy
Population or modelPeoplemultiple correlated randomized substudies measuring cognitive-test performance and DNA-methylation biomarkers
Population/model
3,562 older adults completing web-based assessments
Intervention and comparator
multivitamins; correlated randomized substudies
Duration
Not separately structured in this publication record
Measured outcome
immediate recall, retention, executive function, and object recognition

What the covered evidence found

COSMOS cognitive substudies reported small improvements in some cognitive-test scores, with mixed results across domains. · The three cognitive reports are directionally consistent analyses from one parent COSMOS program rather than three independent replications.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Test-score differences do not establish dementia prevention or preserved independent function. · Shared recruitment and program infrastructure limit independence.

Funding and conflicts: NIH and other support; Pfizer Consumer Healthcare/Haleon supplied some pills and packaging.

Correction/retraction state: none

Connected reporting

Multivitamins moved some tests and aging clocks. What does that mean?

Measured outcome: cognitive-test scores, word recall and DNA-methylation biomarkers

Released conclusion: COSMOS found small cognitive-test differences and modest movement in two DNA-methylation clocks; neither establishes dementia prevention or longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03035201 · NCT04582617

Identifier and correction state checked · projected from seventh-coverage-edition.json

peer-reviewed-multicenter-randomized-follow-up · peer-reviewed

pmid 30824296

DOI 10.1016/j.eururo.2019.02.009

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-multicenter-randomized-follow-up
Study designRandomized trialpeer reviewed multicenter randomized follow up
Population or modelPeopleHuman prostate-cancer mortality and diagnosis · long randomized screening follow-up
Population/model
42,376 men age 55–74 in ERSPC Rotterdam; primary analysis in 34,831 men age 55–69
Intervention and comparator
Invitation to PSA-based screening about every four years versus control
Duration
Median 21-year Rotterdam follow-up
Measured outcome
section-specific screening program · cancer-specific mortality and metastatic disease

What the covered evidence found

The 21-year focal evidence is the Rotterdam ERSPC section using repeated PSA-based screening about every four years. · In the primary age group, prostate-cancer mortality RR was 0.73 (95% CI 0.61–0.88) and metastatic prostate cancer RR was 0.67 (95% CI 0.58–0.78).

What it does not establish

Does not establish the effect of one PSA test or a modern MRI-led pathway. · Does not establish lower all-cause mortality, longer life or net benefit for everyone.

Limitations: Center protocols and contamination differed; this is not a uniform multicenter 21-year estimate. · Cancer-specific mortality was primary; metastatic disease secondary.

Funding and conflicts: Dutch Cancer Society, Netherlands Organisation for Health Research and Development, Dutch Cancer Research Foundation, and an unconditional Beckman-Coulter-Hybritech grant; focal paper reports no author conflicts.

Correction/retraction state: none-found

Connected reporting

PSA screening lowered prostate-cancer mortality—and increased diagnoses

Measured outcome: prostate-cancer mortality, metastasis and diagnoses

Released conclusion: In the primary age group, prostate-cancer mortality was lower with screening (RR 0.73), as was metastatic disease (RR 0.67). Screening also produced 57 excess prostate-cancer diagnoses per 1,000 men randomized.

Boundary: An all-cause survival benefit or favorable balance for every individual.

Identifier and correction state checked · projected from sixteenth-coverage-claim-map.json

peer-reviewed-primary-randomized-section-follow-up · peer-reviewed

pmid 37029074

DOI 10.1016/j.eururo.2023.03.016

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-randomized-section-follow-up
Study designRandomized trialpeer reviewed primary randomized section follow up
Population or modelPeopleHuman prostate-cancer mortality and diagnosis · long randomized screening follow-up
Population/model
42,376 men age 55–74 in ERSPC Rotterdam; primary analysis in 34,831 men age 55–69
Intervention and comparator
Invitation to PSA-based screening about every four years versus control
Duration
Median 21-year Rotterdam follow-up
Measured outcome
section-specific screening program · cancer-specific mortality and metastatic disease · endpoint hierarchy · excess diagnosis and false positives · older-at-randomization cancer-specific mortality

What the covered evidence found

The 21-year focal evidence is the Rotterdam ERSPC section using repeated PSA-based screening about every four years. · In the primary age group, prostate-cancer mortality RR was 0.73 (95% CI 0.61–0.88) and metastatic prostate cancer RR was 0.67 (95% CI 0.58–0.78). · The paper treated all-cause death as competing-risk context rather than demonstrating an all-cause screening effect. · Rotterdam reported 57 excess prostate-cancer diagnoses per 1,000 randomized to screening; across five ERSPC centers, 17.8% of screened men had at least one false positive. · Among men randomized at age 70 or older, prostate-cancer mortality RR was 1.18 (95% CI 0.87–1.62), with no demonstrated difference.

What it does not establish

Does not establish the effect of one PSA test or a modern MRI-led pathway. · Does not establish lower all-cause mortality, longer life or net benefit for everyone. · Does not justify a longevity headline or claim screening extends life. · Does not mean every additional diagnosis is harmful or that cancer-specific benefit erases urinary, sexual and other harms. · Does not prove harm, equivalence or an individualized cutoff.

Limitations: Center protocols and contamination differed; this is not a uniform multicenter 21-year estimate. · Cancer-specific mortality was primary; metastatic disease secondary. · Cancer-specific benefit can coexist with harms and no measured all-cause effect. · Excess diagnosis is not identical to overdiagnosis in every case; biopsy and treatment harms need separate evidence. · Imprecise subgroup estimate from a historical screening pathway.

Funding and conflicts: Dutch Cancer Society, Netherlands Organisation for Health Research and Development, Dutch Cancer Research Foundation, and an unconditional Beckman-Coulter-Hybritech grant; focal paper reports no author conflicts.

Correction/retraction state: none-found

Connected reporting

PSA screening lowered prostate-cancer mortality—and increased diagnoses

Measured outcome: prostate-cancer mortality, metastasis and diagnoses

Released conclusion: In the primary age group, prostate-cancer mortality was lower with screening (RR 0.73), as was metastatic disease (RR 0.67). Screening also produced 57 excess prostate-cancer diagnoses per 1,000 men randomized.

Boundary: An all-cause survival benefit or favorable balance for every individual.

Identifier and correction state checked · projected from sixteenth-coverage-claim-map.json

peer-reviewed-extended-randomized-follow-up · peer-reviewed

pmid 31260833

DOI 10.1016/j.jtho.2019.05.044

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-extended-randomized-follow-up
Study designRandomized trialpeer reviewed extended randomized follow up
Population or modelPeopleHuman lung-cancer mortality · large randomized screening trial
Population/model
53,454 adults age 55–74 with at least 30 pack-years who currently smoked or had quit within 15 years
Intervention and comparator
Three annual low-dose CT screens versus chest radiography
Duration
Original screening analysis plus median 12.3-year mortality follow-up
Measured outcome
lung-cancer and all-cause mortality

What the covered evidence found

At median 12.3 years, lung-cancer deaths were 1,147 versus 1,236 (RR 0.92, 95% CI 0.85–1.00); all-cause difference 4.2 per 1,000 (95% CI −2.6 to 10.9).

What it does not establish

Does not demonstrate a precise all-cause or longevity benefit.

Limitations: Adjusted estimates are secondary; the all-cause interval includes no difference.

Funding and conflicts: NCI/NIH-sponsored; ACRIN/NCI/NIH institutional grants and named outside relationships including LUNGevity, Siemens and Veracyte.

Correction/retraction state: none-found

Connected reporting

Low-dose CT reduced lung-cancer mortality in selected high-risk smokers

Measured outcome: lung-cancer and all-cause mortality

Released conclusion: The original NLST analysis reported 247 versus 309 lung-cancer deaths per 100,000 person-years, a 20% relative reduction with low-dose CT. It did not test never-smokers or the general population.

Boundary: Benefit for never-smokers, average-risk adults or overall lifespan.

Identifier and correction state checked · projected from sixteenth-coverage-claim-map.json

peer-reviewed-related-randomized-trial · peer-reviewed

Urolithin Middle Aged

DOI 10.1016/j.xcrm.2022.100633

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-related-randomized-trial
Study designRandomized trialrelated placebo controlled randomized trial
Population or modelAnimal modelsmall four-month randomized human trial with two null primary outcomes and secondary muscle-endurance and biomarker signals
Population/model
Middle-aged adults in a separate four-month study
Intervention and comparator
urolithin A; small randomized trial
Duration
Not separately structured in this publication record
Measured outcome
Primary peak-power outcome plus secondary strength, exercise and biomarker outcomes

What the covered evidence found

A related middle-aged-adult trial missed its peak-power primary endpoint, and neither trial validates other urolithin A, pomegranate, microbiome or retail formulations.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to a small, short trial in selected older adults from two Seattle sites using one 1,000 mg branded formulation; it cannot establish disability prevention, long-term safety, healthspan or lifespan.

Funding and conflicts: The publication disclosed Amazentis employees, its founder and chief executive, board leadership, company shareholdings, and patent interests. That direct sponsor and intellectual-property involvement must remain visible alongside the short duration and selected study population.

Correction/retraction state: none

Connected reporting

Urolithin A missed both primary outcomes in older adults

Measured outcome: walking distance, muscle endurance and ATP production

Released conclusion: ENERGIZE found no significant benefit for six-minute walk distance or maximal ATP production. Secondary endurance and biomarker signals remain preliminary and do not establish disability prevention or longer healthy life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03283462

Identifier and correction state checked · projected from fifteenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Prosper Primary

DOI 10.1016/S0140-6736(02)11600-X

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplerandomized human trials, subgroup analyses, extended follow-up, and individual-participant meta-analysis
Population/model
5,804 adults aged 70–82 with or at risk of vascular disease
Intervention and comparator
statins; trials and pooled evidence
Duration
Not separately structured in this publication record
Measured outcome
coronary death, nonfatal myocardial infarction, and stroke

What the covered evidence found

In PROSPER's mixed primary- and secondary-prevention population, pravastatin reduced the composite endpoint mainly through coronary outcomes while stroke was neutral. · PROSPER's primary-prevention subgroup and ALLHAT-LLT's older-adult analysis were neutral, while pooled evidence is clearer for older adults with established vascular disease.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The overall result cannot be transferred unchanged to people starting primary prevention after age 75. · ALLHAT-LLT had crossover and modest LDL separation; subgroup and meta-analytic evidence do not replace an adequately powered dedicated trial.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Statin evidence changes with age, risk and prevention setting

Measured outcome: coronary and vascular events, stroke, mortality, cognition and cancer follow-up

Released conclusion: Evidence is clearer after vascular disease than for starting primary prevention after age 75, and it does not establish longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02099123 · NCT04262206

Identifier and correction state checked · projected from sixth-coverage-edition.json

peer-reviewed-multicenter-randomized-follow-up · peer-reviewed

pmid 25108889

DOI 10.1016/S0140-6736(14)60525-0

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-multicenter-randomized-follow-up
Study designRandomized trialpeer reviewed multicenter randomized follow up
Population or modelPeopleHuman prostate-cancer mortality and diagnosis · long randomized screening follow-up
Population/model
42,376 men age 55–74 in ERSPC Rotterdam; primary analysis in 34,831 men age 55–69
Intervention and comparator
Invitation to PSA-based screening about every four years versus control
Duration
Median 21-year Rotterdam follow-up
Measured outcome
section-specific screening program · cancer-specific mortality and metastatic disease

What the covered evidence found

The 21-year focal evidence is the Rotterdam ERSPC section using repeated PSA-based screening about every four years. · In the primary age group, prostate-cancer mortality RR was 0.73 (95% CI 0.61–0.88) and metastatic prostate cancer RR was 0.67 (95% CI 0.58–0.78).

What it does not establish

Does not establish the effect of one PSA test or a modern MRI-led pathway. · Does not establish lower all-cause mortality, longer life or net benefit for everyone.

Limitations: Center protocols and contamination differed; this is not a uniform multicenter 21-year estimate. · Cancer-specific mortality was primary; metastatic disease secondary.

Funding and conflicts: Dutch Cancer Society, Netherlands Organisation for Health Research and Development, Dutch Cancer Research Foundation, and an unconditional Beckman-Coulter-Hybritech grant; focal paper reports no author conflicts.

Correction/retraction state: none-found

Connected reporting

PSA screening lowered prostate-cancer mortality—and increased diagnoses

Measured outcome: prostate-cancer mortality, metastasis and diagnoses

Released conclusion: In the primary age group, prostate-cancer mortality was lower with screening (RR 0.73), as was metastatic disease (RR 0.67). Screening also produced 57 excess prostate-cancer diagnoses per 1,000 men randomized.

Boundary: An all-cause survival benefit or favorable balance for every individual.

Identifier and correction state checked · projected from sixteenth-coverage-claim-map.json

peer-reviewed-primary · peer-reviewed

Finger Primary

DOI 10.1016/S0140-6736(15)60461-5

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplerandomized human cognitive-test evidence for a combined two-year multidomain program
Population/model
1,260 Finnish adults age 60–77 selected for elevated dementia risk
Intervention and comparator
FINGER; randomized multidomain trial
Duration
Not separately structured in this publication record
Measured outcome
two-year neuropsychological-test-battery composite change

What the covered evidence found

In 1,260 at-risk Finnish adults age 60–77, the two-year multidomain package produced a small advantage in NTB-composite change versus general health advice: difference in change per year 0.022 (95% CI 0.002–0.042). · FINGER delivered diet guidance, exercise, cognitive and social activity, and vascular-risk monitoring together. · The FINGER primary report did not establish prevention of dementia, disability, death, healthspan loss, or shorter lifespan. · Reported adverse events were more frequent in the FINGER intervention arm, mainly musculoskeletal pain.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The standardized cognitive-test result applies to the combined program and does not identify a causal component. · The design cannot assign the observed difference to any one component. · Absence of these endpoints in the primary report is an inference boundary, not proof that no effect is possible. · Event reporting does not establish the safety profile of every related lifestyle program.

Funding and conflicts: Public and nonprofit research funding; the primary report lists investigator disclosures and does not establish an intervention-component sponsor effect.

Correction/retraction state: none

Connected reporting

FINGER slightly improved cognitive-test scores. It did not prove dementia prevention

Measured outcome: global cognitive composite and domain tests

Released conclusion: A combined two-year program produced a small cognitive-test advantage; it cannot identify a winning component or establish dementia, disability, mortality, healthspan, or lifespan benefit.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01041989

Identifier and correction state checked · projected from eighth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Achieve Primary

DOI 10.1016/S0140-6736(23)01406-X

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplerandomized human evidence with secondary subgroup analysis
Population/model
977 adults aged 70–84
Intervention and comparator
hearing; randomized trial with subgroup signals
Duration
Not separately structured in this publication record
Measured outcome
three-year global cognition

What the covered evidence found

Across the full ACHIEVE cohort, hearing intervention did not slow three-year global cognitive decline versus health education. · Prespecified recruitment-source and later modeled-risk analyses found larger signals among higher-risk participants. · ACHIEVE does not establish that hearing treatment prevents dementia.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Unmasked trial; cognitive change was not incident dementia. · Subgroup and secondary analyses do not override the null total-cohort primary endpoint. · Incident dementia was not the primary outcome.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Hearing intervention did not slow cognitive decline across the full ACHIEVE trial

Measured outcome: three-year standardized global-cognition change

Released conclusion: The three-year trial was null across its full cohort. Signals in higher-risk groups need confirmation and do not establish dementia prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03243422

Identifier and correction state checked · projected from fifth-coverage-edition.json

peer-reviewed-primary-randomized-follow-up · peer-reviewed

pmid 42102826

DOI 10.1016/S0140-6736(26)00508-8

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-randomized-follow-up
Study designRandomized trialpeer reviewed primary randomized follow up
Population or modelPeopleHuman cancer incidence and mortality · large randomized invitation trial
Population/model
84,583 men and women age 55–64 in Norway, Poland and Sweden
Intervention and comparator
Invitation to one screening colonoscopy versus no screening invitation
Duration
13 years for focal outcomes; 10 years only where explicitly dated
Measured outcome
program offer and participation · colorectal-cancer incidence · colorectal-cancer mortality · modeled outcomes under per-protocol assumptions

What the covered evidence found

NordICC randomized an invitation to one colonoscopy, not guaranteed completion; 42.0% participated in the earlier report. · At 13 years, colorectal-cancer incidence was 375/28,217 (1.46%) versus 912/56,366 (1.80%); RR 0.81 (95% CI 0.71–0.90). · At 13 years, colorectal-cancer mortality was 106/28,217 (0.41%) versus 236/56,366 (0.47%); RR 0.88 (95% CI 0.68–1.08), so reduction was not demonstrated. · Per-protocol estimates were RR 0.55 (95% CI 0.33–0.81) for incidence and RR 0.70 (95% CI 0.26–1.25) for colorectal-cancer mortality.

What it does not establish

Does not show everyone invited underwent colonoscopy or that per-protocol analysis preserves randomization. · Does not establish lower cancer mortality, all-cause mortality, healthspan or lifespan. · Does not establish benefit, harm or all-cause longevity effect. · Does not prove the causal effect every individual would receive from colonoscopy.

Limitations: Intention-to-screen includes nonparticipation. · Uses the current corrected record; subgroup/location claims are excluded. · Lower-than-expected mortality reduced event information; no demonstrated difference is not proof of equivalence. · Depends on compliance and modeling assumptions.

Funding and conflicts: Public and cancer-organization funding; author research support and endoscopy-industry consulting, honoraria or equipment relationships.

Correction/retraction state: published-erratum-linked-pmid-42119586

Connected reporting

A colonoscopy invitation lowered cancer incidence—not mortality at 13 years

Measured outcome: colorectal-cancer incidence and mortality

Released conclusion: At 13 years, colorectal cancer was diagnosed in 1.46% of the invited group and 1.80% of the usual-care group. Colorectal-cancer mortality was 0.41% versus 0.47%; the confidence interval included no difference.

Boundary: A colorectal-cancer mortality or all-cause survival benefit was not demonstrated.

Identifier and correction state checked · projected from sixteenth-coverage-claim-map.json

peer-reviewed-primary · peer-reviewed

Isaacc Cpap

DOI 10.1016/S2213-2600(19)30271-1

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplelarge human randomized evidence with null intention-to-treat cardiovascular primary outcomes and separate symptom benefits
Population/model
1,264 adults with acute coronary syndrome and obstructive sleep apnea without sleepiness
Intervention and comparator
CPAP; large randomized trials
Duration
Not separately structured in this publication record
Measured outcome
cardiovascular events over median 3.35 years

What the covered evidence found

In ISAACC, cardiovascular events occurred in 16% of the CPAP group and 17% of usual care; the hazard ratio was 0.89 (95% CI 0.68–1.17). · The major SAVE and ISAACC intention-to-treat trials did not demonstrate fewer major cardiovascular events, and neither was a lifespan trial.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The trial enrolled non-sleepy patients after acute coronary syndrome, average CPAP use was 2.78 hours per night and generalizability is limited. · Null intention-to-treat cardiovascular results do not show that diagnosed sleep apnea should go untreated or settle every adherence-sensitive subgroup question.

Funding and conflicts: SAVE reported support from public agencies and Philips Respironics; ISAACC reported public and industry support. Treatment adherence and selected populations limit inference.

Correction/retraction state: none

Connected reporting

CPAP improved symptoms—not cardiovascular events in major trials

Measured outcome: major cardiovascular events, sleepiness, symptoms and quality of life

Released conclusion: SAVE and ISAACC did not significantly reduce their primary cardiovascular outcomes; SAVE separately found symptom and quality-of-life benefits.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00738179 · NCT01335087

Identifier and correction state checked · projected from eleventh-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Nr Pilot

DOI 10.1038/s41467-018-03421-7

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized crossover trial
Population or modelPeopleearly randomized human biomarker and short-term physiological evidence; no lifespan evidence
Population/model
24 completers
Intervention and comparator
NAD biology; small trials
Duration
Not separately structured in this publication record
Measured outcome
NAD metabolites and exploratory physiology

What the covered evidence found

Oral NR changed NAD-related metabolites in small human trials. · Featured NR trials did not show broad metabolic, mitochondrial, motor, or cognitive benefit. · No featured NAD-precursor evidence establishes longer healthy-human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Target engagement does not establish meaningful clinical benefit. · Trials were small, short and heterogeneous. · Compounds, routes and formulations are not interchangeable.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

NAD precursors raise some metabolites; human longevity benefits remain unproven

Measured outcome: metabolites, physiology and short-term function

Released conclusion: Small trials show target engagement, not broad clinical, healthspan or lifespan benefit—and products and routes are not interchangeable.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02835664 · NCT02921659 · NCT04823260

Identifier and correction state checked · projected from fourth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Tre Timing

DOI 10.1038/s41591-024-03375-y

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeopleshort randomized human evidence
Population/model
197 adults with overweight or obesity
Intervention and comparator
meal timing; short randomized trials
Duration
Not separately structured in this publication record
Measured outcome
12-week MRI visceral fat and safety

What the covered evidence found

Other short trials reported comparator-specific weight or blood-pressure signals but no consistent visceral-fat benefit. · These time-restricted-eating trials did not test biological aging, healthspan, mortality or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Timing, counseling, energy restriction, populations and endpoints differed. · Absence of a measured endpoint cannot be converted into benefit or harm.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Human time-restricted-eating trials show mixed short-term results—not slower aging

Measured outcome: weight, body composition, visceral fat and cardiometabolic markers

Released conclusion: Different eating windows and comparators produced different weight and fat findings; none tested biological aging, healthspan or lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03393195 · NCT03459703 · NCT05310721

Identifier and correction state checked · projected from fifth-coverage-edition.json

peer-reviewed-biomarker-secondary · peer-reviewed

Cosmos Epigenetic Clocks

DOI 10.1038/s41591-026-04239-3

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-biomarker-secondary
Study designRandomized trialrandomized trial biomarker substudy
Population or modelPeoplemultiple correlated randomized substudies measuring cognitive-test performance and DNA-methylation biomarkers
Population/model
958 COSMOS participants with serial blood samples
Intervention and comparator
multivitamins; correlated randomized substudies
Duration
Not separately structured in this publication record
Measured outcome
five DNA-methylation clocks over two years

What the covered evidence found

A 2026 COSMOS analysis found modest movement in two DNA-methylation clocks, but did not establish better clinical aging, lower mortality, or longer life.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Five clocks were tested and biomarker age-equivalence is not an observed clinical outcome.

Funding and conflicts: NIH and other support; Pfizer Consumer Healthcare/Haleon supplied some pills and packaging.

Correction/retraction state: none

Connected reporting

Multivitamins moved some tests and aging clocks. What does that mean?

Measured outcome: cognitive-test scores, word recall and DNA-methylation biomarkers

Released conclusion: COSMOS found small cognitive-test differences and modest movement in two DNA-methylation clocks; neither establishes dementia prevention or longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03035201 · NCT04582617

Identifier and correction state checked · projected from seventh-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Horizon Pft

DOI 10.1056/NEJMoa067312

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplelarge randomized human fracture evidence plus outcome-specific duration and current regulator safety context
Population/model
7,765 postmenopausal women with osteoporosis, mean age about 73
Intervention and comparator
zoledronic acid; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
morphometric vertebral, hip and other fracture outcomes over three years

What the covered evidence found

In 7,765 postmenopausal women with osteoporosis, three annual zoledronic-acid infusions reduced new morphometric vertebral fractures from 10.9% to 3.3% (RR 0.30, 95% CI 0.24–0.38). · Hip fractures occurred in 1.4% with zoledronic acid versus 2.5% with placebo (HR 0.59) in HORIZON-PFT. · Bone-mineral-density and bone-turnover-marker changes support interpretation but are not substitutes for fracture outcomes. · Serious atrial fibrillation, acute-phase symptoms, renal effects and current FDA warnings require visible context when reporting zoledronic-acid benefits. · Zoledronic-acid fracture reduction in osteoporosis does not establish slowed aging, healthspan extension or lifespan extension. · HORIZON was sponsored by Novartis with company involvement and author relationships disclosed in the reports.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The result applies to a defined osteoporosis population and a morphometric vertebral endpoint, not low-risk prevention or aging itself. · Hip-fracture results are distinct from vertebral, nonvertebral, BMD and longevity outcomes. · A biomarker change cannot be relabeled as a clinical fracture, healthspan, mortality or lifespan result. · Trial adverse events and regulator warnings are population- and context-specific and do not provide individualized risk or dosing advice. · Clinically meaningful fracture outcomes still cannot be converted into unmeasured longevity or biological-age outcomes. · Funding and involvement are context for appraisal; they do not by themselves validate or invalidate the randomized results.

Funding and conflicts: Novartis sponsored HORIZON, with company involvement and author relationships disclosed in the primary reports.

Correction/retraction state: none

Connected reporting

Zoledronic acid reduced fractures in osteoporosis—not aging itself

Measured outcome: vertebral, hip and nonvertebral fractures plus bone density

Released conclusion: HORIZON reduced vertebral and hip fractures in postmenopausal osteoporosis, with outcome-specific duration and safety limits—not evidence of slower aging.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00049829 · NCT00145327

Identifier and correction state checked · projected from ninth-coverage-edition.json

peer-reviewed-primary-randomized-trial · peer-reviewed

pmid 21714641

DOI 10.1056/NEJMoa1102873

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-randomized-trial
Study designRandomized trialpeer reviewed primary randomized trial
Population or modelPeopleHuman lung-cancer mortality · large randomized screening trial
Population/model
53,454 adults age 55–74 with at least 30 pack-years who currently smoked or had quit within 15 years
Intervention and comparator
Three annual low-dose CT screens versus chest radiography
Duration
Original screening analysis plus median 12.3-year mortality follow-up
Measured outcome
eligibility and external validity · lung-cancer mortality · absolute lung-cancer mortality rate · positive and false-positive screens · lung-cancer and all-cause mortality · dated population recommendation

What the covered evidence found

NLST studied selected high-risk current/former smokers, not the general population or never-smokers. · Original lung-cancer mortality was 247 versus 309 per 100,000 person-years; relative reduction 20.0% (95% CI 6.8%–26.7%). · The original absolute lung-cancer mortality rates were 247 and 309 deaths per 100,000 person-years. · Across rounds, 24.2% of LDCT and 6.9% of radiography screens were positive; 96.4% and 94.5% of positives were false positives under the trial definition. · At median 12.3 years, lung-cancer deaths were 1,147 versus 1,236 (RR 0.92, 95% CI 0.85–1.00); all-cause difference 4.2 per 1,000 (95% CI −2.6 to 10.9). · Current 2021 USPSTF guidance covers age 50–80, at least 20 pack-years, current smoking or quitting within 15 years, and stop conditions—different from NLST.

What it does not establish

Does not generalize benefit outside a validated eligibility envelope. · Does not show a 20% all-cause mortality reduction or individual benefit. · Does not supply a personalized absolute benefit. · Does not mean 96.4% of all screened people had a false positive or that modern rates are identical. · Does not demonstrate a precise all-cause or longevity benefit. · Does not prescribe screening or replace an individual clinical decision.

Limitations: Original eligibility was narrower than current USPSTF eligibility. · Comparator was chest radiography; relative results need absolute rates and extended follow-up. · Person-year rates are not an individual's cumulative probability. · Trial definitions and management predate current protocols. · Adjusted estimates are secondary; the all-cause interval includes no difference. · Guidance can change and considers preference, health status and ability to undergo treatment.

Funding and conflicts: NCI/NIH-sponsored; ACRIN/NCI/NIH institutional grants and named outside relationships including LUNGevity, Siemens and Veracyte.

Correction/retraction state: none-found

Connected reporting

Low-dose CT reduced lung-cancer mortality in selected high-risk smokers

Measured outcome: lung-cancer and all-cause mortality

Released conclusion: The original NLST analysis reported 247 versus 309 lung-cancer deaths per 100,000 person-years, a 20% relative reduction with low-dose CT. It did not test never-smokers or the general population.

Boundary: Benefit for never-smokers, average-risk adults or overall lifespan.

Identifier and correction state checked · projected from sixteenth-coverage-claim-map.json

peer-reviewed-primary · peer-reviewed

Fluzone High Dose Rct

DOI 10.1056/NEJMoa1315727

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplelarge randomized influenza-illness evidence plus current product-category public-health guidance
Population/model
31,989 adults age 65 or older across the 2011–2012 and 2012–2013 influenza seasons
Intervention and comparator
influenza vaccine; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
protocol-defined laboratory-confirmed influenza with illness, immunogenicity and safety

What the covered evidence found

Across two influenza seasons in adults age 65 or older, protocol-defined laboratory-confirmed influenza occurred in 228 of 15,991 high-dose recipients (1.4%) and 301 of 15,998 standard-dose recipients (1.9%). · The randomized high-dose trial reported 24.2% relative efficacy (95% CI 9.7–36.5) over standard-dose vaccine, alongside an absolute difference of about 0.5 percentage points in observed illness rates. · Serious adverse events occurred in 8.3% of high-dose recipients and 9.0% of standard-dose recipients in the randomized influenza trial. · Higher antibody responses in the high-dose trial do not by themselves establish broader immune rejuvenation, fewer deaths or longer life. · The high-dose influenza trial did not establish slower aging, greater healthspan or longer human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Absolute rates depend on the studied seasons, circulating strains, case definition and enrolled population and may differ in another season. · The relative estimate must remain paired with absolute outcomes and does not compare high-dose vaccine with every current enhanced formulation. · Similar serious-event proportions do not exclude uncommon risks and do not make reactogenicity or every adverse outcome identical. · Immunogenicity is a biomarker outcome and cannot replace the clinical influenza endpoint, mortality or lifespan. · The trial tested influenza illness and safety over two seasons, not a longevity endpoint.

Funding and conflicts: Sanofi funded the high-dose trial and had primary responsibility for design, monitoring, data collection, analysis and statistics.

Correction/retraction state: none

Connected reporting

High-dose flu vaccine reduced influenza—not immune aging

Measured outcome: laboratory-confirmed influenza, immunogenicity and safety

Released conclusion: The randomized result was 1.4% versus 1.9% influenza across two seasons, not proof of immune rejuvenation or longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01427309

Identifier and correction state checked · projected from tenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Zoe 50

DOI 10.1056/NEJMoa1501184

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplestrong randomized shingles-prevention evidence with emerging observational and quasi-experimental dementia evidence
Population/model
15,411 evaluable adults age 50 or older
Intervention and comparator
shingles vaccine; randomized and non-randomized evidence
Duration
Not separately structured in this publication record
Measured outcome
laboratory and clinically confirmed herpes zoster over mean 3.2 years plus solicited and serious adverse events

What the covered evidence found

In ZOE-50 adults age 50 or older, recombinant zoster vaccine produced 6 herpes-zoster cases versus 210 with placebo over a mean 3.2 years, corresponding to 97.2% vaccine efficacy (95% CI 93.7–99.0). · Grade-3 solicited symptoms occurred in 17.0% of recombinant-zoster-vaccine recipients versus 3.2% with placebo, while serious adverse events, potential immune-mediated disease and deaths were similar in ZOE-50. · The featured shingles-vaccine studies do not establish slower biological aging, greater healthspan or longer human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The randomized endpoint was herpes zoster, not dementia, mortality, healthspan or lifespan; applicability to excluded or differently treated populations is not established. · The trial was not large enough to exclude every rare adverse event and its safety follow-up does not establish safety for every population. · Disease prevention and diagnosis timing cannot be substituted for a measured lifespan outcome.

Funding and conflicts: GSK funded ZOE-50. The recombinant-dementia EHR study had NIHR/Wellcome/JDRF support and disclosed one author's GSK consultancy and Oxford–GSK role; GSK was reported uninvolved. The Welsh study reported public and philanthropic grants and no competing interests.

Correction/retraction state: none

Connected reporting

Shingles vaccines prevent shingles. Dementia evidence remains non-randomized

Measured outcome: herpes-zoster disease and recorded dementia diagnoses

Released conclusion: Randomized trials established shingles prevention. Dementia findings come from observational and quasi-experimental studies and do not prove prevention.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01165177

Identifier and correction state checked · projected from tenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Ttrials Main

DOI 10.1056/NEJMoa1506119

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialcoordinated randomized trials
Population or modelAnimal modelhuman randomized evidence for domain-specific function outcomes, with no direct disability, healthspan, mortality, or lifespan endpoint
Population/model
790 symptomatic men age 65 or older with two morning testosterone concentrations averaging below 275 ng/dL
Intervention and comparator
testosterone; one-year randomized trials
Duration
Not separately structured in this publication record
Measured outcome
Sexual function, six-minute walk physical function, vitality, mood, and short-term safety over one year

What the covered evidence found

The Testosterone Trials enrolled 790 symptomatic men age 65 or older with two morning testosterone concentrations averaging below 275 ng/dL and treated them with monitored 1% gel or placebo for one year. · Among men enrolled in the Physical Function Trial, the primary threshold of increasing six-minute walk distance by at least 50 meters did not differ significantly; odds ratio 1.42, P=0.20. · Across all Testosterone Trials participants, 20.5% assigned testosterone and 12.6% assigned placebo improved six-minute walk distance by at least 50 meters, P=0.003. · Across all participants, the mean between-group six-minute walk-distance difference was 6.69 meters; secondary analyses describe the mobility effect as modest and found no difference in falls. · Testosterone produced a moderate sexual-function benefit but no significant benefit on the Vitality Trial primary endpoint; these domains must not be bundled into a general rejuvenation claim. · The one-year Testosterone Trials do not establish frailty reversal, disability prevention, dementia prevention, healthspan extension, or lifespan extension, and were too small for broad long-term safety conclusions.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Applies to selected symptomatic men age 65 or older with repeated low testosterone treated with monitored 1% gel for one year; modest functional results do not establish disability prevention or anti-aging efficacy.

Funding and conflicts: The Testosterone Trials were principally publicly supported, with study product and additional support disclosed by investigators; the trials were not large or long enough for broad safety conclusions.

Correction/retraction state: none

Connected reporting

Testosterone’s walking result was modest—not an anti-aging effect

Measured outcome: six-minute walking distance and a 50-meter improvement threshold

Released conclusion: The prespecified Physical Function Trial threshold was not significant in its enrolled subgroup; broader secondary walking results do not establish disability prevention, healthspan or longevity.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00799617

Identifier and correction state checked · projected from twelfth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Save Cpap

DOI 10.1056/NEJMoa1606599

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplelarge human randomized evidence with null intention-to-treat cardiovascular primary outcomes and separate symptom benefits
Population/model
2,717 adults age 45 to 75 with obstructive sleep apnea and cardiovascular or cerebrovascular disease
Intervention and comparator
CPAP; large randomized trials
Duration
Not separately structured in this publication record
Measured outcome
composite serious cardiovascular events plus symptoms and quality of life

What the covered evidence found

In SAVE, primary cardiovascular events occurred in 17.0% of participants assigned CPAP plus usual care and 15.4% assigned usual care alone; the adjusted hazard ratio was 1.10 (95% CI 0.91–1.32). · SAVE reported improvements in sleepiness, quality of life, mood and work attendance with CPAP despite the null primary cardiovascular result. · The major SAVE and ISAACC intention-to-treat trials did not demonstrate fewer major cardiovascular events, and neither was a lifespan trial.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Participants had established cardiovascular or cerebrovascular disease, mean CPAP use was 3.3 hours per night and the result does not cover all OSA populations. · Secondary symptom outcomes answer a different question from major cardiovascular events and cannot be promoted to longevity evidence. · Null intention-to-treat cardiovascular results do not show that diagnosed sleep apnea should go untreated or settle every adherence-sensitive subgroup question.

Funding and conflicts: SAVE reported support from public agencies and Philips Respironics; ISAACC reported public and industry support. Treatment adherence and selected populations limit inference.

Correction/retraction state: none

Connected reporting

CPAP improved symptoms—not cardiovascular events in major trials

Measured outcome: major cardiovascular events, sleepiness, symptoms and quality of life

Released conclusion: SAVE and ISAACC did not significantly reduce their primary cardiovascular outcomes; SAVE separately found symptom and quality-of-life benefits.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00738179 · NCT01335087

Identifier and correction state checked · projected from eleventh-coverage-edition.json

corrected-primary-paper · peer-reviewed

Predimed Corrected 2018

DOI 10.1056/NEJMoa1800389

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedcorrected-primary-paper
Study designRandomized trialmulticenter randomized dietary trial with corrected analyses for allocation deviations
Population or modelPeoplecorrected/re-published randomized human cardiovascular-outcome trial
Population/model
7,447 high-cardiovascular-risk adults aged 55–80 in Spain without cardiovascular disease at enrollment
Intervention and comparator
Mediterranean diet; corrected randomized trial
Duration
Not separately structured in this publication record
Measured outcome
myocardial infarction; stroke; cardiovascular death; composite cardiovascular event

What the covered evidence found

In corrected PREDIMED analyses, high-risk adults assigned to either supplemented Mediterranean dietary program had fewer composite cardiovascular events than control. · PREDIMED does not establish that a Mediterranean dietary pattern slows biological aging or extends healthy-human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: known/suspected allocation deviations · context-specific interventions · free supplement foods · not an aging or lifespan trial · allocation deviations · context-specific programs · composite outcome · not an aging endpoint · cardiovascular prevention may still affect long-term health but was not a lifespan test

Funding and conflicts: Instituto de Salud Carlos III, Spanish Ministry of Health, and others; free olive oil or nuts provided

Correction/retraction state: corrected

Connected reporting

Applicable registry records: ISRCTN35739639

Identifier and correction state checked · projected from third-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Aspree Primary

DOI 10.1056/NEJMoa1800722

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized double blind placebo controlled trial
Population or modelPeoplelarge human randomized primary-prevention evidence over median 4.7 years
Population/model
19,114 community-dwelling older adults in Australia and the United States, generally age 70 or older (65 or older for Black and Hispanic US participants), without cardiovascular disease, dementia or independence-limiting physical disability at enrollment
Intervention and comparator
low-dose aspirin; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
Disability-free survival composite and components over median 4.7 years

What the covered evidence found

ASPREE randomized 19,114 selected community-dwelling older adults without cardiovascular disease, dementia or independence-limiting disability to 100 mg daily enteric-coated aspirin or placebo. · The disability-free-survival composite occurred at 21.5 events per 1,000 person-years with aspirin and 21.2 with placebo; HR 1.01, 95% CI 0.92 to 1.11. · Disability-free survival combined death, dementia and persistent physical disability and is not equivalent to lifespan or any one component. · Assigned-treatment adherence in the final trial year was 62.1% with aspirin and 64.1% with placebo. · Major hemorrhage occurred in 3.8% with aspirin and 2.8% with placebo; HR 1.38, 95% CI 1.18 to 1.62.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Applies to ASPREE's selected primary-prevention population, 100 mg daily enteric-coated aspirin versus placebo, median 4.7 years randomized follow-up and incomplete late adherence; it does not determine secondary-prevention benefit or an individual medication decision.

Funding and conflicts: ASPREE was supported by US and Australian public/institutional funders; Bayer supplied aspirin and matching placebo in kind and was reported to have no other trial role. The 2026 follow-up discloses author grants and several outside pharmaceutical relationships.

Correction/retraction state: none

Connected reporting

ASPREE found no gain in disability-free survival—and more major bleeding

Measured outcome: disability-free survival · major bleeding

Released conclusion: In 19,114 selected older adults, daily low-dose aspirin did not improve the trial’s composite of death, dementia or persistent physical disability over a median 4.7 years. Major hemorrhage was higher.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01038583

Identifier and correction state checked · projected from thirteenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Aspree Mortality

DOI 10.1056/NEJMoa1803955

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial secondary and post hoc analysis
Population or modelPeoplerandomized-period secondary mortality evidence plus trial-derived observational extension follow-up
Population/model
19,114 community-dwelling older adults in Australia and the United States, generally age 70 or older (65 or older for Black and Hispanic US participants), without cardiovascular disease, dementia or independence-limiting physical disability at enrollment
Intervention and comparator
low-dose aspirin; randomized trial plus observational extension
Duration
Not separately structured in this publication record
Measured outcome
All-cause and cause-specific mortality over median 4.7 years

What the covered evidence found

All-cause mortality was 12.7 per 1,000 person-years with aspirin and 11.1 with placebo; HR 1.14, 95% CI 1.01 to 1.29. · Cancer-related death in the randomized period occurred in 3.1% with aspirin and 2.3% with placebo; HR 1.31, 95% CI 1.10 to 1.56. · The randomized-period mortality and cancer signal was a secondary, unexpected finding that the investigators said should be interpreted cautiously.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Applies to ASPREE's selected primary-prevention population, 100 mg daily enteric-coated aspirin versus placebo, median 4.7 years randomized follow-up and incomplete late adherence; it does not determine secondary-prevention benefit or an individual medication decision.

Funding and conflicts: ASPREE was supported by US and Australian public/institutional funders; Bayer supplied aspirin and matching placebo in kind and was reported to have no other trial role. The 2026 follow-up discloses author grants and several outside pharmaceutical relationships.

Correction/retraction state: none

Connected reporting

ASPREE’s cancer signal changed across longer follow-up

Measured outcome: cancer mortality · long-term follow-up

Released conclusion: The randomized trial found an unexpected cancer-mortality imbalance. Longer follow-up found no difference in overall cancer incidence and no post-trial mortality legacy effect.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01038583

Identifier and correction state checked · projected from thirteenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Aspree Cardiovascular

DOI 10.1056/NEJMoa1805819

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial prespecified secondary analysis
Population or modelPeoplelarge human randomized evidence for prespecified cardiovascular and bleeding outcomes
Population/model
19,114 community-dwelling older adults in Australia and the United States, generally age 70 or older (65 or older for Black and Hispanic US participants), without cardiovascular disease, dementia or independence-limiting physical disability at enrollment
Intervention and comparator
low-dose aspirin; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
Cardiovascular composite and major hemorrhage over median 4.7 years

What the covered evidence found

The cardiovascular composite rate was 10.7 per 1,000 person-years with aspirin and 11.3 with placebo; HR 0.95, 95% CI 0.83 to 1.08. · The cardiovascular composite included fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure. · Major hemorrhage occurred at 8.6 per 1,000 person-years with aspirin and 6.2 with placebo; HR 1.38, 95% CI 1.18 to 1.62. · Major hemorrhage included hemorrhagic stroke, symptomatic intracranial bleeding, or qualifying extracranial bleeding requiring major care or causing death. · ASPREE studied primary prevention; its findings do not erase aspirin's established uses for selected people with cardiovascular disease or prior events.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Applies to ASPREE's selected primary-prevention population, 100 mg daily enteric-coated aspirin versus placebo, median 4.7 years randomized follow-up and incomplete late adherence; it does not determine secondary-prevention benefit or an individual medication decision.

Funding and conflicts: ASPREE was supported by US and Australian public/institutional funders; Bayer supplied aspirin and matching placebo in kind and was reported to have no other trial role. The 2026 follow-up discloses author grants and several outside pharmaceutical relationships.

Correction/retraction state: none

Connected reporting

ASPREE did not lower cardiovascular events—and increased major bleeding

Measured outcome: cardiovascular events · major bleeding

Released conclusion: In selected older adults without cardiovascular disease, low-dose aspirin did not significantly reduce the trial’s cardiovascular composite. Major hemorrhage occurred more often.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01038583

Identifier and correction state checked · projected from thirteenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Vital Vitamin D Primary

DOI 10.1056/NEJMoa1809944

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplelarge randomized human cancer, cardiovascular, and fracture outcome evidence
Population/model
25,871 generally healthy US adults
Intervention and comparator
vitamin D; large randomized prevention trial
Duration
Not separately structured in this publication record
Measured outcome
invasive cancer and major cardiovascular events

What the covered evidence found

In VITAL's generally healthy population, vitamin D3 did not significantly reduce invasive cancer or major cardiovascular events. · VITAL did not establish that vitamin D supplementation slows biological aging or extends healthspan or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The trial was not a treatment study for diagnosed vitamin D deficiency. · The absence of direct longevity endpoints is not proof that no effect can exist.

Funding and conflicts: Primarily NIH-funded; vitamin D was donated by Pharmavite.

Correction/retraction state: none

Connected reporting

Vitamin D is essential. VITAL still found no broad prevention benefit

Measured outcome: invasive cancer, major cardiovascular events and clinical fractures

Released conclusion: In generally healthy adults, vitamin D3 did not significantly reduce invasive cancer, major cardiovascular events, or fractures; deficiency treatment is a different question.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01169259 · NCT01704859

Identifier and correction state checked · projected from seventh-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Vital Omega

DOI 10.1056/NEJMoa1811403

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplelarge randomized human cardiovascular-outcomes trials with formulation-specific results and current regulatory context
Population/model
25,871 US adults in cardiovascular primary prevention
Intervention and comparator
omega-3; formulation-specific randomized trials
Duration
Not separately structured in this publication record
Measured outcome
major cardiovascular events and cancer

What the covered evidence found

VITAL and OMEMI were neutral for their primary cardiovascular outcomes, although VITAL reported a lower secondary myocardial-infarction component. · Prescription icosapent ethyl, mixed EPA and DHA trial products, dietary fish, and retail supplements are not interchangeable; none of the featured trials demonstrated slower aging or longer life.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The trials used different populations, products, doses, and comparators; VITAL's component result was not multiplicity-adjusted. · A population-specific cardiovascular outcome does not establish a healthspan or lifespan effect.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

“Omega-3” is not one intervention—and the trial results do not transfer

Measured outcome: cardiovascular composites and components, mortality, atrial fibrillation and bleeding

Released conclusion: Two mixed EPA+DHA trials were neutral on primary outcomes; prescription icosapent ethyl benefited a defined high-risk population with safety and comparator limits.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01169259 · NCT01492361 · NCT01841944

Identifier and correction state checked · projected from sixth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Reduce It

DOI 10.1056/NEJMoa1812792

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplelarge randomized human cardiovascular-outcomes trials with formulation-specific results and current regulatory context
Population/model
8,179 statin-treated adults with elevated triglycerides and high cardiovascular risk
Intervention and comparator
omega-3; formulation-specific randomized trials
Duration
Not separately structured in this publication record
Measured outcome
ischemic cardiovascular events and safety

What the covered evidence found

Prescription icosapent ethyl reduced cardiovascular events in REDUCE-IT's statin-treated high-risk population and was associated with more atrial-fibrillation hospitalization and a numerical increase in serious bleeding. · Prescription icosapent ethyl, mixed EPA and DHA trial products, dietary fish, and retail supplements are not interchangeable; none of the featured trials demonstrated slower aging or longer life.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Mineral oil as comparator creates uncertainty about effect size, and all-cause mortality was not significantly lower. · A population-specific cardiovascular outcome does not establish a healthspan or lifespan effect.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

“Omega-3” is not one intervention—and the trial results do not transfer

Measured outcome: cardiovascular composites and components, mortality, atrial fibrillation and bleeding

Released conclusion: Two mixed EPA+DHA trials were neutral on primary outcomes; prescription icosapent ethyl benefited a defined high-risk population with safety and comparator limits.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01169259 · NCT01492361 · NCT01841944

Identifier and correction state checked · projected from sixth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Sprint Final

DOI 10.1056/NEJMoa1901281

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplelarge randomized human cardiovascular-outcomes evidence with secondary and post-trial cognitive follow-up
Population/model
9,361 high-risk adults without diabetes or prior stroke
Intervention and comparator
blood pressure; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
cardiovascular events, mortality, and treatment harms

What the covered evidence found

In SPRINT's eligible high-risk population, intensive systolic blood-pressure treatment reduced the randomized trial's primary cardiovascular composite and all-cause mortality. · Intensive treatment increased serious hypotension, electrolyte abnormalities, and acute kidney injury or failure, while injurious falls were similar.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The population excluded people with diabetes or prior stroke, used standardized automated office measurements, and did not establish a universal target. · Trial event rates do not predict an individual person's balance of benefit and harm.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

SPRINT reduced cardiovascular events—not aging itself

Measured outcome: cardiovascular events, mortality, adverse events and cognitive outcomes

Released conclusion: Intensive treatment lowered cardiovascular events and mortality in eligible high-risk adults, with more hypotension, electrolyte problems and kidney injury.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01206062

Identifier and correction state checked · projected from sixth-coverage-edition.json

peer-reviewed-independent-randomized-trial · peer-reviewed

pmid 31995683

DOI 10.1056/NEJMoa1911793

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-independent-randomized-trial
Study designRandomized trialpeer reviewed independent randomized trial
Population or modelPeopleHuman lung-cancer mortality · large randomized screening trial
Population/model
53,454 adults age 55–74 with at least 30 pack-years who currently smoked or had quit within 15 years
Intervention and comparator
Three annual low-dose CT screens versus chest radiography
Duration
Original screening analysis plus median 12.3-year mortality follow-up
Measured outcome
lung-cancer mortality

What the covered evidence found

Original lung-cancer mortality was 247 versus 309 per 100,000 person-years; relative reduction 20.0% (95% CI 6.8%–26.7%).

What it does not establish

Does not show a 20% all-cause mortality reduction or individual benefit.

Limitations: Comparator was chest radiography; relative results need absolute rates and extended follow-up.

Funding and conflicts: NCI/NIH-sponsored; ACRIN/NCI/NIH institutional grants and named outside relationships including LUNGevity, Siemens and Veracyte.

Correction/retraction state: none-found

Connected reporting

Low-dose CT reduced lung-cancer mortality in selected high-risk smokers

Measured outcome: lung-cancer and all-cause mortality

Released conclusion: The original NLST analysis reported 247 versus 309 lung-cancer deaths per 100,000 person-years, a 20% relative reduction with low-dose CT. It did not test never-smokers or the general population.

Boundary: Benefit for never-smokers, average-risk adults or overall lifespan.

Identifier and correction state checked · projected from sixteenth-coverage-claim-map.json

peer-reviewed-primary · peer-reviewed

Vital Vitamin D Fractures

DOI 10.1056/NEJMoa2202106

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial ancillary
Population or modelPeoplelarge randomized human cancer, cardiovascular, and fracture outcome evidence
Population/model
VITAL participants not selected for deficiency, low bone mass, or osteoporosis
Intervention and comparator
vitamin D; large randomized prevention trial
Duration
Not separately structured in this publication record
Measured outcome
total, nonvertebral, and hip fractures

What the covered evidence found

Vitamin D3 did not significantly reduce total, nonvertebral, or hip fractures in the VITAL ancillary trial. · VITAL did not establish that vitamin D supplementation slows biological aging or extends healthspan or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Participants were not selected for deficiency, low bone mass, or osteoporosis. · The absence of direct longevity endpoints is not proof that no effect can exist.

Funding and conflicts: Primarily NIH-funded; vitamin D was donated by Pharmavite.

Correction/retraction state: none

Connected reporting

Vitamin D is essential. VITAL still found no broad prevention benefit

Measured outcome: invasive cancer, major cardiovascular events and clinical fractures

Released conclusion: In generally healthy adults, vitamin D3 did not significantly reduce invasive cancer, major cardiovascular events, or fractures; deficiency treatment is a different question.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01169259 · NCT01704859

Identifier and correction state checked · projected from seventh-coverage-edition.json

peer-reviewed-primary-randomized-trial · peer-reviewed

pmid 36214590

DOI 10.1056/NEJMoa2208375

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-randomized-trial
Study designRandomized trialpeer reviewed primary randomized trial
Population or modelPeopleHuman cancer incidence and mortality · large randomized invitation trial
Population/model
84,583 men and women age 55–64 in Norway, Poland and Sweden
Intervention and comparator
Invitation to one screening colonoscopy versus no screening invitation
Duration
13 years for focal outcomes; 10 years only where explicitly dated
Measured outcome
program offer and participation · short-term screening harms · all-cause mortality and current guidance

What the covered evidence found

NordICC randomized an invitation to one colonoscopy, not guaranteed completion; 42.0% participated in the earlier report. · The 10-year report recorded 15 major bleeding events after polyp removal and no perforation or screening-related death within 30 days. · At 10 years, all-cause mortality was 11.03% versus 11.04% (RR 0.99, 95% CI 0.96–1.04); no 13-year all-cause claim is authorized.

What it does not establish

Does not show everyone invited underwent colonoscopy or that per-protocol analysis preserves randomization. · Does not prove colonoscopy is risk-free or quantify personalized risk. · Does not establish longer life or select a strategy for an individual.

Limitations: Intention-to-screen includes nonparticipation. · Dated 10-year context and 30-day window do not capture every downstream or uncommon harm. · Earlier follow-up only; guidance includes multiple screening options.

Funding and conflicts: Public and cancer-organization funding; author research support and endoscopy-industry consulting, honoraria or equipment relationships.

Correction/retraction state: none-found

Connected reporting

A colonoscopy invitation lowered cancer incidence—not mortality at 13 years

Measured outcome: colorectal-cancer incidence and mortality

Released conclusion: At 13 years, colorectal cancer was diagnosed in 1.46% of the invited group and 1.80% of the usual-care group. Colorectal-cancer mortality was 0.41% versus 0.47%; the confidence interval included no difference.

Boundary: A colorectal-cancer mortality or all-cause survival benefit was not demonstrated.

Identifier and correction state checked · projected from sixteenth-coverage-claim-map.json

peer-reviewed-primary · peer-reviewed

Aresvi 006

DOI 10.1056/NEJMoa2209604

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplethree large randomized product-specific trials plus maturing durability and postauthorization safety evidence
Population/model
24,966 adults age 60 or older in an international phase 3 trial
Intervention and comparator
RSV vaccines; three randomized vaccine trials
Duration
Not separately structured in this publication record
Measured outcome
RT-PCR-confirmed RSV lower-respiratory-tract disease, acute respiratory infection and safety over the first season

What the covered evidence found

In the Arexvy pivotal trial, RSV lower-respiratory-tract disease occurred in 7 of 12,467 vaccine recipients and 40 of 12,499 placebo recipients over median 6.7 months; efficacy was 82.6% (96.95% CI 57.9–94.1). · Separate Arexvy, Abrysvo and mResvia trials do not establish a head-to-head product ranking because case definitions, populations, follow-up and analysis times differ. · The featured RSV trials do not establish slower immune aging, lower all-cause mortality, greater healthspan or longer human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The first-season estimate used the trial's case definition; severe-outcome estimates had few events and do not establish mortality benefit. · Cross-trial percentages are descriptive only; CDC currently expresses no product preference. · Trial-defined respiratory-disease prevention cannot be substituted for mortality, healthspan or lifespan outcomes.

Funding and conflicts: The Arexvy, Abrysvo and mResvia pivotal trials were funded by GSK, Pfizer and Moderna, respectively; current guidance and postauthorization safety context come from CDC and FDA.

Correction/retraction state: none

Connected reporting

RSV vaccines reduce respiratory disease. Separate trials cannot rank them

Measured outcome: RSV lower-respiratory disease or illness, acute respiratory disease and safety

Released conclusion: Arexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT04886596 · NCT05035212 · NCT05127434

Identifier and correction state checked · projected from tenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Renoir

DOI 10.1056/NEJMoa2213836

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplethree large randomized product-specific trials plus maturing durability and postauthorization safety evidence
Population/model
34,284 adults age 60 or older in an international phase 3 trial
Intervention and comparator
RSV vaccines; three randomized vaccine trials
Duration
Not separately structured in this publication record
Measured outcome
RSV lower-respiratory-tract illness by two- and three-symptom definitions, acute respiratory illness and safety

What the covered evidence found

In the Abrysvo pivotal trial, efficacy was 66.7% (95% CI 28.8–85.8) against RSV lower-respiratory-tract illness with at least two symptoms and 85.7% (95% CI 32.0–98.7) with at least three symptoms. · Separate Arexvy, Abrysvo and mResvia trials do not establish a head-to-head product ranking because case definitions, populations, follow-up and analysis times differ. · The featured RSV trials do not establish slower immune aging, lower all-cause mortality, greater healthspan or longer human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The three-symptom estimate was based on 2 versus 14 cases, and its definition and follow-up are not interchangeable with other products' trials. · Cross-trial percentages are descriptive only; CDC currently expresses no product preference. · Trial-defined respiratory-disease prevention cannot be substituted for mortality, healthspan or lifespan outcomes.

Funding and conflicts: The Arexvy, Abrysvo and mResvia pivotal trials were funded by GSK, Pfizer and Moderna, respectively; current guidance and postauthorization safety context come from CDC and FDA.

Correction/retraction state: none

Connected reporting

RSV vaccines reduce respiratory disease. Separate trials cannot rank them

Measured outcome: RSV lower-respiratory disease or illness, acute respiratory disease and safety

Released conclusion: Arexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT04886596 · NCT05035212 · NCT05127434

Identifier and correction state checked · projected from tenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Traverse Cardiovascular

DOI 10.1056/NEJMoa2215025

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized noninferiority trial
Population or modelPeoplelarge human randomized noninferiority evidence for one cardiovascular composite, with limited duration and separate safety signals
Population/model
5,246 men age 45 to 80 with symptoms, two fasting testosterone values below 300 ng/dL, and preexisting or high cardiovascular risk
Intervention and comparator
testosterone; large randomized noninferiority trial
Duration
Not separately structured in this publication record
Measured outcome
Time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke

What the covered evidence found

TRAVERSE enrolled 5,246 men age 45 to 80 with hypogonadal symptoms, two fasting testosterone concentrations below 300 ng/dL, and preexisting or high cardiovascular risk. · The primary MACE outcome occurred in 182 of 2,601 men (7.0%) assigned testosterone and 190 of 2,603 (7.3%) assigned placebo; hazard ratio 0.96, 95% CI 0.78 to 1.17. · TRAVERSE met its prespecified cardiovascular noninferiority criterion because the upper 95% confidence boundary was below 1.5; this does not show cardiovascular benefit. · TRAVERSE reported mean treatment duration of about 21.7 months and mean follow-up of about 33 months, limiting inference about very-long-term safety. · Atrial fibrillation, acute kidney injury, and pulmonary embolism occurred more often in the testosterone group; the report does not by itself establish a named causal mechanism. · TRAVERSE was funded by AbbVie and other testosterone manufacturers in an FDA-required postmarketing program, with the sponsor role disclosed in the primary report. · Cardiovascular noninferiority in TRAVERSE does not establish mortality benefit, disability prevention, healthspan extension, or lifespan extension.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Applies to selected symptomatic men age 45 to 80 with two fasting low-testosterone measurements, elevated cardiovascular risk, monitored transdermal 1.62% gel, and about 33 months mean follow-up; it does not establish every safety outcome or longer-term effects.

Funding and conflicts: TRAVERSE was an FDA-required postmarketing trial funded by an industry consortium led by AbbVie; sponsor and investigator roles require visible disclosure.

Correction/retraction state: none

Connected reporting

TRAVERSE found cardiovascular noninferiority—not a longevity benefit

Measured outcome: major cardiovascular events and cardiovascular safety outcomes

Released conclusion: Among selected men with hypogonadism and elevated cardiovascular risk, testosterone gel was noninferior to placebo for major cardiovascular events; the trial did not test longer life or general anti-aging use.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03518034

Identifier and correction state checked · projected from twelfth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Mind Primary

DOI 10.1056/NEJMoa2302368

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplerandomized human cognitive and MRI evidence against an active calorie-restricted dietary control
Population/model
604 adults age 65+ without cognitive impairment and with family dementia history, overweight and suboptimal diet
Intervention and comparator
MIND diet; randomized dietary trial
Duration
Not separately structured in this publication record
Measured outcome
three-year global cognition and MRI measures

What the covered evidence found

The MIND intervention did not significantly outperform the active control for three-year global cognition: difference 0.035 standardized units (95% CI -0.022 to 0.092; p=.23). · Both MIND trial groups received counseling, a 250-kcal-per-day restriction goal, and weight-loss support, and both improved. · Prespecified MRI measures were similar between MIND and active-control groups. · Observational MIND-diet associations cannot supersede the randomized primary comparison; the trial did not test dementia prevention or lifespan. · The MIND randomized trial was funded by the National Institute on Aging and disclosed donated foods and product support.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: A null between-group result does not prove that no possible effect exists in any population or implementation. · The trial did not compare the MIND pattern with no behavior change. · Structural MRI measures are not equivalent to dementia incidence, daily function, mortality, healthspan, or lifespan. · This boundary does not invalidate observational work; it limits the conclusion supported by this randomized trial. · Funding and material support are disclosed neutrally and do not by themselves establish bias.

Funding and conflicts: National Institute on Aging funding; investigators disclosed donated foods and product support.

Correction/retraction state: none

Connected reporting

The MIND diet trial found no cognitive edge over its active control

Measured outcome: global cognition and structural MRI measures

Released conclusion: Both groups improved with counseling and calorie restriction; the between-group cognitive difference was not significant and MRI measures were similar.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02817074

Identifier and correction state checked · projected from eighth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Conquerrsv

DOI 10.1056/NEJMoa2307079

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplethree large randomized product-specific trials plus maturing durability and postauthorization safety evidence
Population/model
35,541 adults age 60 or older in a phase 2–3 trial
Intervention and comparator
RSV vaccines; three randomized vaccine trials
Duration
Not separately structured in this publication record
Measured outcome
RSV lower-respiratory-tract disease by two- and three-symptom definitions, acute respiratory disease and safety

What the covered evidence found

In the mResvia pivotal analysis, efficacy was 83.7% (95.88% CI 66.0–92.2) against RSV lower-respiratory-tract disease with at least two symptoms and 82.4% (96.36% CI 34.8–95.3) with at least three symptoms. · Separate Arexvy, Abrysvo and mResvia trials do not establish a head-to-head product ranking because case definitions, populations, follow-up and analysis times differ. · The featured RSV trials do not establish slower immune aging, lower all-cause mortality, greater healthspan or longer human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Median follow-up at primary analysis was 112 days; longer-term protection waned and the trial was not powered for mortality. · Cross-trial percentages are descriptive only; CDC currently expresses no product preference. · Trial-defined respiratory-disease prevention cannot be substituted for mortality, healthspan or lifespan outcomes.

Funding and conflicts: The Arexvy, Abrysvo and mResvia pivotal trials were funded by GSK, Pfizer and Moderna, respectively; current guidance and postauthorization safety context come from CDC and FDA.

Correction/retraction state: none

Connected reporting

RSV vaccines reduce respiratory disease. Separate trials cannot rank them

Measured outcome: RSV lower-respiratory disease or illness, acute respiratory disease and safety

Released conclusion: Arexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT04886596 · NCT05035212 · NCT05127434

Identifier and correction state checked · projected from tenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Select

DOI 10.1056/NEJMoa2307563

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized outcomes trial
Population or modelPeoplerandomized disease-outcome evidence and approved population-specific cardiovascular indication
Population/model
17,604 adults with CVD and BMI at least 27, without diabetes
Intervention and comparator
GLP-1 drugs; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
major cardiovascular events

What the covered evidence found

Semaglutide reduced SELECT's major cardiovascular event composite in its enrolled population. · SELECT did not test aging reversal, healthspan, or lifespan extension.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Established CVD, BMI at least 27, no diabetes; not a healthy-aging population. · Absence of an aging endpoint is not proof of no future effect; it is a current evidence boundary.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Semaglutide reduced cardiovascular events in SELECT—not aging

Measured outcome: major cardiovascular events and safety

Released conclusion: The randomized result and approved indication are population-specific; anti-aging, healthspan and lifespan claims were not tested.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03574597

Identifier and correction state checked · projected from fourth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Traverse Fracture

DOI 10.1056/NEJMoa2308836

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial substudy
Population or modelPeoplelarge randomized clinical-fracture evidence contrasted with an earlier small one-year bone-density surrogate substudy
Population/model
5,204 TRAVERSE participants with adjudicated clinical-fracture follow-up
Intervention and comparator
testosterone; randomized trials
Duration
Not separately structured in this publication record
Measured outcome
Time to first clinical fracture over median 3.19 years

What the covered evidence found

The TRAVERSE fracture analysis included 5,204 participants and followed them for a median 3.19 years. · A clinical fracture occurred in 91 of 2,601 participants (3.50%) assigned testosterone and 64 of 2,603 (2.46%) assigned placebo; hazard ratio 1.43, 95% CI 1.04 to 1.97. · Testosterone treatment did not reduce clinical fractures in TRAVERSE; fracture incidence was higher in the testosterone group. · An improvement in bone-density or estimated-strength surrogates cannot be substituted for the later randomized clinical-fracture outcome. · The fracture result does not establish why fractures were higher and does not justify a specific mechanistic, disability, healthspan, or lifespan claim.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Applies to the adjudicated TRAVERSE fracture substudy over median 3.19 years; it does not identify why fractures differed or establish effects for other formulations, populations, or longer follow-up. · One-year volumetric BMD and estimated strength are surrogate measurements in a small substudy; they are not clinical fractures and cannot establish disability, healthspan, or lifespan benefit.

Funding and conflicts: TRAVERSE was an FDA-required postmarketing trial funded by an industry consortium led by AbbVie; sponsor and investigator roles require visible disclosure. The Testosterone Trials were principally publicly supported, with study product and additional support disclosed by investigators; the trials were not large or long enough for broad safety conclusions.

Correction/retraction state: none

Connected reporting

Testosterone did not prevent fractures in TRAVERSE

Measured outcome: clinical fractures and bone-density measures

Released conclusion: Clinical fractures were more frequent with testosterone than placebo in TRAVERSE; a smaller substudy’s bone-density gain cannot substitute for fracture outcomes.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00799617 · NCT03518034

Identifier and correction state checked · projected from twelfth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Nr Obesity

DOI 10.1093/ajcn/nqaa072

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized crossover trial
Population or modelPeopleearly randomized human biomarker and short-term physiological evidence; no lifespan evidence
Population/model
13 overweight or obese adults
Intervention and comparator
NAD biology; small trials
Duration
Not separately structured in this publication record
Measured outcome
metabolic physiology and NAD metabolites

What the covered evidence found

Oral NR changed NAD-related metabolites in small human trials. · Featured NR trials did not show broad metabolic, mitochondrial, motor, or cognitive benefit. · No featured NAD-precursor evidence establishes longer healthy-human lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Target engagement does not establish meaningful clinical benefit. · Trials were small, short and heterogeneous. · Compounds, routes and formulations are not interchangeable.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

NAD precursors raise some metabolites; human longevity benefits remain unproven

Measured outcome: metabolites, physiology and short-term function

Released conclusion: Small trials show target engagement, not broad clinical, healthspan or lifespan benefit—and products and routes are not interchangeable.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02835664 · NCT02921659 · NCT04823260

Identifier and correction state checked · projected from fourth-coverage-edition.json

peer-reviewed-primary-randomized-trial · peer-reviewed

Glynac Older Adults

DOI 10.1093/gerona/glac135

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary-randomized-trial
Study designRandomized trialsmall placebo controlled randomized trial
Population or modelPeoplevery small short randomized human biomarker and function study with numerous outcomes and explicitly exploratory aging-hallmark analyses
Population/model
24 older adults age 61 to 80 with BMI above 27 kg/m2, randomized 12 per arm
Intervention and comparator
GlyNAC; very small randomized trial
Duration
Not separately structured in this publication record
Measured outcome
Sixteen-week registered glutathione outcome plus many metabolic, function and exploratory aging-hallmark measures

What the covered evidence found

The GlyNAC trial randomized 24 older adults age 61 to 80 with BMI above 27 kg/m2, 12 per arm, to glycine 100 mg/kg/day plus N-acetylcysteine 100 mg/kg/day or isonitrogenous alanine for 16 weeks. · The registry identifies muscle glutathione concentration as the primary outcome, while the publication reports many metabolic, vascular, body-composition, physical-function and aging-hallmark measures. · Six-minute walk distance changed from 522.5 to 564.8 m in the active arm, P=.053, and 518.3 to 527.1 m in placebo, P=.99; within-arm changes are not a confirmed randomized between-group benefit. · The many reported outcomes create a multiplicity problem, and aging-hallmark analyses added after trial completion were explicitly exploratory rather than evidence of reversing biological aging. · An independent 114-person dose-ranging study lasted two weeks and measured glutathione redox and oxidative damage; it does not replicate the 16-week trial's broad function or aging-hallmark claims. · No supplement-related adverse events were reported and monitored liver and kidney markers were stable over 16 weeks, but 12 treated older adults cannot establish uncommon or long-term harms, aging reversal, healthspan or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to a 12-per-arm, sixteen-week comparison with many measured outcomes and selected participants; it cannot establish aging reversal, disease or disability prevention, healthspan or lifespan.

Funding and conflicts: The publication disclosed NIH/NIA grant R01AG041782 and a McNair Foundation philanthropic gift, stated that funders had no role, and declared no conflicts of interest. Those are reported disclosures rather than proof that all potential bias is absent.

Correction/retraction state: none

Connected reporting

GlyNAC’s small trial cannot establish reversal of aging

Measured outcome: biomarkers and physical function

Released conclusion: A 16-week study randomized 24 older adults—12 per arm—and reported many biomarker and function measures. Its size, multiplicity and exploratory analyses do not prove that GlyNAC reverses aging or extends healthspan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01870193

Identifier and correction state checked · projected from fifteenth-coverage-edition.json

primary-paper · peer-reviewed

Metformin Tissue Crossover

DOI 10.1111/acel.12723

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designRandomized trialrandomized double blind placebo controlled crossover
Population or modelPeoplesmall human mechanistic/function trials; no healthy-human longevity trial result
Population/model
14 approximately 70-year-old participants
Intervention and comparator
metformin; small trials
Duration
Not separately structured in this publication record
Measured outcome
glucose and insulin responses; muscle and adipose gene expression

What the covered evidence found

The reviewed human evidence does not establish that metformin extends lifespan in healthy people.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: very small sample · short exposure · mechanistic endpoints · no clinical outcome · condition-specific diabetes evidence and ongoing trials answer different questions

Funding and conflicts: paper funding and disclosures required

Correction/retraction state: none

Connected reporting

Metformin is established for diabetes—not for extending healthy human life

Measured outcome: muscle adaptation, metabolism and gene expression

Released conclusion: Small older-adult studies show mechanistic changes and a blunted hypertrophy signal, not healthspan or lifespan extension.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02308228 · NCT03107884

Identifier and correction state checked · projected from third-coverage-edition.json

primary-paper · peer-reviewed

Masters Metformin Training

DOI 10.1111/acel.13039

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-paper
Study designRandomized trialrandomized double blind placebo controlled multicenter trial
Population or modelPeoplesmall human mechanistic/function trials; no healthy-human longevity trial result
Population/model
94 healthy adults aged 65 or older during 14 weeks of supervised progressive resistance training
Intervention and comparator
metformin; small trials
Duration
Not separately structured in this publication record
Measured outcome
lean mass; thigh muscle mass; muscle area and density; strength

What the covered evidence found

During 14 weeks of supervised resistance training in healthy adults aged 65 or older, the metformin group gained less lean and thigh muscle mass than placebo. · The reviewed human evidence does not establish that metformin extends lifespan in healthy people.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: short duration · healthy selected volunteers · training-adaptation endpoints · not a morbidity or lifespan trial · short trial · selected volunteers · hypertrophy is not healthspan · strength difference was not statistically significant · condition-specific diabetes evidence and ongoing trials answer different questions

Funding and conflicts: NIA R01AG046920 and NCATS UL1TR001998/UL1TR003096; paper disclosures required

Correction/retraction state: none

Connected reporting

Metformin is established for diabetes—not for extending healthy human life

Measured outcome: muscle adaptation, metabolism and gene expression

Released conclusion: Small older-adult studies show mechanistic changes and a blunted hypertrophy signal, not healthspan or lifespan extension.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02308228 · NCT03107884

Identifier and correction state checked · projected from third-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Short Melatonin Trial

DOI 10.1111/j.1365-2869.2007.00613.x

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplehuman randomized evidence for modest sleep outcomes, with product-specific limits and no direct human longevity endpoint
Population/model
354 adults age 55 to 80 with primary insomnia
Intervention and comparator
melatonin; product-specific randomized trials
Duration
Not separately structured in this publication record
Measured outcome
sleep quality and morning alertness after prolonged-release melatonin

What the covered evidence found

A separate trial in adults age 55 to 80 reported improved sleep quality and morning alertness with prolonged-release melatonin. · The featured human trials measured sleep outcomes, not biological-age reversal, healthspan, mortality or lifespan extension.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The short trial evaluated a particular prolonged-release product and subjective outcomes, not mortality or biological aging. · Mechanistic interest and circadian biology cannot substitute for randomized human evidence on aging or longevity outcomes.

Funding and conflicts: The featured prolonged-release melatonin trial was funded by Neurim; several authors disclosed employee, consultant, owner or leadership roles. Product formulation and jurisdiction matter.

Correction/retraction state: none

Connected reporting

Melatonin can shift sleep outcomes—not human aging

Measured outcome: sleep latency, sleep quality and morning alertness

Released conclusion: Specific prolonged-release melatonin trials reported modest sleep benefits; they did not test biological-age reversal, healthspan or lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00397189

Identifier and correction state checked · projected from eleventh-coverage-edition.json

peer-reviewed-follow-up · peer-reviewed

Active Ten Year

DOI 10.1111/jgs.12607

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-follow-up
Study designRandomized trialrandomized follow up
Population or modelPeoplerandomized trained-ability evidence plus long-term function, mortality and contested claims-based dementia analyses
Population/model
ACTIVE participants followed for trained abilities and everyday function through ten years
Intervention and comparator
cognitive training; randomized trial plus disputed secondary analysis
Duration
Not separately structured in this publication record
Measured outcome
trained-domain persistence and instrumental daily-activity outcomes

What the covered evidence found

ACTIVE memory, reasoning and speed training improved specifically trained abilities; ten-year persistence was detectable for reasoning and speed, not memory. · At ten years, ACTIVE intervention groups reported less decline in instrumental daily activities, while self-reported and performance-based function remained distinct.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Performance on trained domains is not proof of generalized cognitive rejuvenation. · The follow-up does not guarantee preserved independence for an individual.

Funding and conflicts: NIH-supported trial and follow-ups; the 20-year mortality report declared no conflicts, while commercial descendants are not evidence for the studied protocol.

Correction/retraction state: none

Connected reporting

Cognitive training improved practiced skills—not survival or proven dementia prevention

Measured outcome: trained abilities, daily function, all-cause mortality and claims-diagnosed dementia

Released conclusion: ACTIVE supports trained-ability gains and some function signals, found no mortality benefit, and leaves a claims-based dementia subgroup methodologically disputed.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00298558

Identifier and correction state checked · projected from eighth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Omemi

DOI 10.1161/CIRCULATIONAHA.120.052209

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplelarge randomized human cardiovascular-outcomes trials with formulation-specific results and current regulatory context
Population/model
1,027 adults aged 70–82 after myocardial infarction
Intervention and comparator
omega-3; formulation-specific randomized trials
Duration
Not separately structured in this publication record
Measured outcome
composite cardiovascular events, atrial fibrillation, and bleeding

What the covered evidence found

VITAL and OMEMI were neutral for their primary cardiovascular outcomes, although VITAL reported a lower secondary myocardial-infarction component. · Prescription icosapent ethyl, mixed EPA and DHA trial products, dietary fish, and retail supplements are not interchangeable; none of the featured trials demonstrated slower aging or longer life.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The trials used different populations, products, doses, and comparators; VITAL's component result was not multiplicity-adjusted. · A population-specific cardiovascular outcome does not establish a healthspan or lifespan effect.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

“Omega-3” is not one intervention—and the trial results do not transfer

Measured outcome: cardiovascular composites and components, mortality, atrial fibrillation and bleeding

Released conclusion: Two mixed EPA+DHA trials were neutral on primary outcomes; prescription icosapent ethyl benefited a defined high-risk population with safety and comparator limits.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01169259 · NCT01492361 · NCT01841944

Identifier and correction state checked · projected from sixth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Creatine Men

DOI 10.1177/0260106020975247

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial analysis
Population or modelPeoplesystematic review plus randomized human trials
Population/model
38 older men
Intervention and comparator
creatine; trials and pooled evidence
Duration
Not separately structured in this publication record
Measured outcome
one-year bone, muscle, strength and adverse events

What the covered evidence found

One-year creatine-plus-training reports found selected imaging differences, while the older-male analysis found no added bone, lean-tissue or strength benefit. · The featured creatine evidence does not establish better independent function, healthspan, mortality or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Small analyses; exact funding and product supply were not reported in accessible primary metadata. · Trials measured muscle, bone, strength and safety markers, not longevity.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Applicable registry records: NCT01057680

Identifier and correction state checked · projected from fifth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Prolonged Release Melatonin

DOI 10.1186/1741-7015-8-51

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplehuman randomized evidence for modest sleep outcomes, with product-specific limits and no direct human longevity endpoint
Population/model
791 adults with primary insomnia, including a prespecified older subgroup age 65 to 80
Intervention and comparator
melatonin; product-specific randomized trials
Duration
Not separately structured in this publication record
Measured outcome
sleep latency, sleep quality, morning alertness and safety

What the covered evidence found

In the prolonged-release melatonin trial, the prespecified age-65-to-80 subgroup had a reported sleep-latency difference of 15.6 minutes versus placebo (95% CI 6.0–25.3 minutes faster). · The featured human trials measured sleep outcomes, not biological-age reversal, healthspan, mortality or lifespan extension.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This was a subgroup in a specific formulation trial; it does not generalize to every supplement, dose, timing schedule or insomnia cause. · Mechanistic interest and circadian biology cannot substitute for randomized human evidence on aging or longevity outcomes.

Funding and conflicts: The featured prolonged-release melatonin trial was funded by Neurim; several authors disclosed employee, consultant, owner or leadership roles. Product formulation and jurisdiction matter.

Correction/retraction state: none

Connected reporting

Melatonin can shift sleep outcomes—not human aging

Measured outcome: sleep latency, sleep quality and morning alertness

Released conclusion: Specific prolonged-release melatonin trials reported modest sleep benefits; they did not test biological-age reversal, healthspan or lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00397189

Identifier and correction state checked · projected from eleventh-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Kjaer Resveratrol Metabolic Syndrome

DOI 10.1210/jc.2016-2160

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplesmall randomized human trials dominated by cognitive tests and metabolic or cardiovascular surrogate endpoints
Population/model
74 men with metabolic syndrome
Intervention and comparator
resveratrol; small heterogeneous trials
Duration
Not separately structured in this publication record
Measured outcome
metabolic outcomes and laboratory safety signals

What the covered evidence found

Several controlled resveratrol trials found no meaningful improvement in metabolic or cardiovascular surrogate outcomes in their tested populations. · Current human resveratrol trials do not establish longer life or healthspan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Trials used different doses, durations, formulations, and populations. · Animal and mechanistic evidence is indirect for human longevity.

Funding and conflicts: Mixed investigator, public, and public-private support; some study products were manufacturer supplied.

Correction/retraction state: none

Connected reporting

Resveratrol has a longevity reputation. Human trials tell a mixed story

Measured outcome: memory tests, metabolic markers, body composition, inflammation and exercise adaptation

Released conclusion: One small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01150955 · NCT01364961 · NCT01412645

Identifier and correction state checked · projected from seventh-coverage-edition.json

peer-reviewed-secondary · peer-reviewed

Creatine Imaging

DOI 10.1249/MSS.0000000000002722

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-secondary
Study designRandomized trialrandomized trial secondary analysis
Population or modelPeoplesystematic review plus randomized human trials
Population/model
70 adults, mean age 58
Intervention and comparator
creatine; trials and pooled evidence
Duration
Not separately structured in this publication record
Measured outcome
one-year bone area and muscle density

What the covered evidence found

One-year creatine-plus-training reports found selected imaging differences, while the older-male analysis found no added bone, lean-tissue or strength benefit. · The featured creatine evidence does not establish better independent function, healthspan, mortality or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Small analyses; exact funding and product supply were not reported in accessible primary metadata. · Trials measured muscle, bone, strength and safety markers, not longevity.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Applicable registry records: NCT01057680

Identifier and correction state checked · projected from fifth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Made Resveratrol Crossover

DOI 10.1371/journal.pone.0118393

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized crossover trial
Population or modelPeoplesmall randomized human trials dominated by cognitive tests and metabolic or cardiovascular surrogate endpoints
Population/model
45 overweight or slightly obese adults
Intervention and comparator
resveratrol; small heterogeneous trials
Duration
Not separately structured in this publication record
Measured outcome
lipid, glucose, inflammation, and endothelial markers

What the covered evidence found

Several controlled resveratrol trials found no meaningful improvement in metabolic or cardiovascular surrogate outcomes in their tested populations.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Trials used different doses, durations, formulations, and populations.

Funding and conflicts: Mixed investigator, public, and public-private support; some study products were manufacturer supplied.

Correction/retraction state: none

Connected reporting

Resveratrol has a longevity reputation. Human trials tell a mixed story

Measured outcome: memory tests, metabolic markers, body composition, inflammation and exercise adaptation

Released conclusion: One small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01150955 · NCT01364961 · NCT01412645

Identifier and correction state checked · projected from seventh-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Witte Resveratrol Memory

DOI 10.1523/JNEUROSCI.0385-14.2014

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplesmall randomized human trials dominated by cognitive tests and metabolic or cardiovascular surrogate endpoints
Population/model
healthy overweight older adults
Intervention and comparator
resveratrol; small heterogeneous trials
Duration
Not separately structured in this publication record
Measured outcome
memory-test performance, glucose metabolism, and hippocampal connectivity

What the covered evidence found

One small 26-week resveratrol trial reported improved memory-test performance in healthy overweight older adults. · Current human resveratrol trials do not establish longer life or healthspan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Small sample, narrow population, and surrogate/test endpoints make this early formulation-specific evidence. · Animal and mechanistic evidence is indirect for human longevity.

Funding and conflicts: Mixed investigator, public, and public-private support; some study products were manufacturer supplied.

Correction/retraction state: none

Connected reporting

Resveratrol has a longevity reputation. Human trials tell a mixed story

Measured outcome: memory tests, metabolic markers, body composition, inflammation and exercise adaptation

Released conclusion: One small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01150955 · NCT01364961 · NCT01412645

Identifier and correction state checked · projected from seventh-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Poulsen High Dose Resveratrol

DOI 10.2337/db12-0975

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplesmall randomized human trials dominated by cognitive tests and metabolic or cardiovascular surrogate endpoints
Population/model
24 obese men
Intervention and comparator
resveratrol; small heterogeneous trials
Duration
Not separately structured in this publication record
Measured outcome
insulin sensitivity, substrate metabolism, and body composition

What the covered evidence found

Several controlled resveratrol trials found no meaningful improvement in metabolic or cardiovascular surrogate outcomes in their tested populations. · Current human resveratrol trials do not establish longer life or healthspan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Trials used different doses, durations, formulations, and populations. · Animal and mechanistic evidence is indirect for human longevity.

Funding and conflicts: Mixed investigator, public, and public-private support; some study products were manufacturer supplied.

Correction/retraction state: none

Connected reporting

Resveratrol has a longevity reputation. Human trials tell a mixed story

Measured outcome: memory tests, metabolic markers, body composition, inflammation and exercise adaptation

Released conclusion: One small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01150955 · NCT01364961 · NCT01412645

Identifier and correction state checked · projected from seventh-coverage-edition.json

peer-reviewed-independent-randomized-trial · peer-reviewed

Glynac Independent Dose Ranging

DOI 10.3389/fragi.2022.852569

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-independent-randomized-trial
Study designRandomized trialindependent short randomized dose ranging trial
Population or modelPeoplevery small short randomized human biomarker and function study with numerous outcomes and explicitly exploratory aging-hallmark analyses
Population/model
114 healthy volunteers including older adults across three fixed GlyNAC doses
Intervention and comparator
GlyNAC; very small randomized trial
Duration
Not separately structured in this publication record
Measured outcome
Two-week glutathione redox and oxidative-damage measures rather than longer-term function

What the covered evidence found

An independent 114-person dose-ranging study lasted two weeks and measured glutathione redox and oxidative damage; it does not replicate the 16-week trial's broad function or aging-hallmark claims.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to a 12-per-arm, sixteen-week comparison with many measured outcomes and selected participants; it cannot establish aging reversal, disease or disability prevention, healthspan or lifespan.

Funding and conflicts: The publication disclosed NIH/NIA grant R01AG041782 and a McNair Foundation philanthropic gift, stated that funders had no role, and declared no conflicts of interest. Those are reported disclosures rather than proof that all potential bias is absent.

Correction/retraction state: none

Connected reporting

GlyNAC’s small trial cannot establish reversal of aging

Measured outcome: biomarkers and physical function

Released conclusion: A 16-week study randomized 24 older adults—12 per arm—and reported many biomarker and function measures. Its size, multiplicity and exploratory analyses do not prove that GlyNAC reverses aging or extends healthspan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01870193

Identifier and correction state checked · projected from fifteenth-coverage-edition.json

peer-reviewed-pharmacokinetic-randomized-trial · peer-reviewed

Spermidine Pk Crossover

DOI 10.3390/nu15081852

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-pharmacokinetic-randomized-trial
Study designRandomized trialsmall randomized crossover pharmacokinetic trial
Population or modelPeoplephase 2b randomized human cognitive-outcome evidence with a null primary result and only exploratory verbal-memory and inflammation signals
Population/model
12 healthy adults receiving 15 mg/day spermidine or placebo for five days
Intervention and comparator
wheat-germ spermidine extract; small randomized phase 2b trial
Duration
Not separately structured in this publication record
Measured outcome
Plasma and salivary polyamines rather than cognitive or clinical outcomes

What the covered evidence found

A separate 12-person five-day crossover trial using 15 mg/day did not raise plasma or salivary spermidine, although plasma spermine increased; it did not test cognition.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: This claim is limited to one single-center trial in selected older adults with subjective cognitive decline, one wheat-germ extract, one dose and twelve months; it cannot establish dementia prevention, broad cognitive benefit, healthspan or lifespan.

Funding and conflicts: German federal and academic support was disclosed. Several authors reported equity, executive or advisory roles, patents, or former equity involving Longevity Labs GmbH, which also supported development of the spermidine-rich extract; the paper states that funders had no role in trial conduct or reporting.

Correction/retraction state: none

Connected reporting

Spermidine did not improve the trial’s primary memory outcome

Measured outcome: memory and cognitive tests

Released conclusion: In the 12-month SmartAge trial, a wheat-germ spermidine extract did not improve the prespecified memory outcome or secondary outcomes. Exploratory signals do not establish dementia prevention or longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT03094546

Identifier and correction state checked · projected from fifteenth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Late Life Cbti

DOI 10.5665/sleep.4008

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized trial
Population or modelPeoplehuman randomized evidence for sleep outcomes, with no direct longevity or dementia endpoint
Population/model
123 older adults with chronic primary insomnia
Intervention and comparator
CBT-I; randomized behavioral trials
Duration
Not separately structured in this publication record
Measured outcome
sleep outcomes and remission after behavioral treatment

What the covered evidence found

A separate 123-person late-life insomnia trial found clinically meaningful sleep improvement after behavioral treatment in the population studied. · The featured CBT-I trials measured sleep outcomes, not biological aging, dementia incidence, mortality, healthspan or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Results apply to the studied older adults and sleep outcomes; they do not establish prevention of neurodegeneration or longer life. · Absence of a longevity endpoint cannot be converted into evidence for or against lifespan extension.

Funding and conflicts: The featured CBT-I trials reported public or academic support; the evidence does not establish dementia prevention or longer life.

Correction/retraction state: none

Connected reporting

CBT-I improves later-life insomnia—not aging itself

Measured outcome: sleep latency, sleep efficiency, insomnia remission and durability

Released conclusion: Two randomized trials support meaningful sleep improvement in older adults; they did not test dementia prevention, biological aging or lifespan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT00280020 · NCT00295386

Identifier and correction state checked · projected from eleventh-coverage-edition.json

primary-randomized-report · peer-reviewed

ACCORD intensive glycemia outcomes

PMID 18539917

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-randomized-report
Study designRandomized trialprimary randomized report
Population or modelPeopleLarge randomized cardiovascular-outcome trial with an early-stopped intensive glycemia arm
Population/model
Adults with established type 2 diabetes plus cardiovascular disease or added risk factors
Intervention and comparator
Intensive multi-drug glycemia target strategy versus standard strategy · Intensive versus standard glycemia strategy · Intensive versus standard glycemia strategy · Different intensive and standard glucose-control strategies
Duration
Mean 3.5 years before intensive-arm stop · Mean 3.5 years · Mean 3.5 years · Active trial and later analyses
Measured outcome
HbA1c target and achieved levels; Nonfatal myocardial infarction, nonfatal stroke or cardiovascular death; All-cause mortality; Safety and applicability

What the covered evidence found

ACCORD randomized 10,251 high-risk adults with type 2 diabetes to multi-drug strategies targeting HbA1c below 6.0% or 7.0–7.9%; achieved medians were 6.4% and 7.5%. · The primary cardiovascular outcome occurred in 352 versus 371 participants; hazard ratio 0.90, P=0.16. · Deaths were 257 versus 203; hazard ratio 1.22, P=0.04, prompting early discontinuation of intensive therapy. · Assistance-requiring hypoglycemia and weight gain over 10 kg were more frequent; hypoglycemia did not explain the mortality difference and a different intensive strategy in ADVANCE did not increase mortality.

What it does not establish

No effect estimate for people without diabetes or any single treatment · No statistically significant reduction in major cardiovascular events · No claim that lower glucose, diabetes care, diet or exercise generally increases mortality · No single causal mechanism or cross-trial efficacy ranking

Limitations: Selected high-risk population and multi-drug strategy · Intensive arm stopped early · Mechanism unresolved and strategy-specific; later excess attenuated · Mechanism remains unresolved and trials differ materially

Funding and conflicts: NHLBI/NIH/CDC support; manufacturers supplied medicines/equipment and multiple author industry relationships were disclosed.

Correction/retraction state: none-linked-as-of-2026-08-26

Connected reporting

ACCORD’s intensive glucose target increased mortality and was stopped early

Measured outcome: major cardiovascular events, all-cause mortality and treatment harms

Released conclusion: The primary cardiovascular outcome was not significantly lower (352 versus 371 events; hazard ratio 0.90; P=0.16). Deaths were higher with intensive treatment (257 versus 203; hazard ratio 1.22; P=0.04), prompting early discontinuation.

Boundary: ACCORD does not show that all glucose lowering is harmful; it tested one intensive, multi-drug target strategy in a high-risk population.

Applicable registry records: NCT00000620

Identifier and correction state checked · projected from seventeenth-coverage-claim-map.json

peer-reviewed-secondary · peer-reviewed

Prosper Cognition

PMID 19653027

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-secondary
Study designRandomized trialrandomized trial secondary analysis
Population or modelPeoplerandomized human trials, subgroup analyses, extended follow-up, and individual-participant meta-analysis
Population/model
PROSPER cognitive substudy participants
Intervention and comparator
statins; trials and pooled evidence
Duration
Not separately structured in this publication record
Measured outcome
cognitive performance

What the covered evidence found

The featured statin evidence did not establish better cognition, less disability, all-cause survival, or longer human lifespan, and two dedicated older-adult trials had no posted results.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Absence of posted results is not evidence of no effect; the trial registries are context only.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Statin evidence changes with age, risk and prevention setting

Measured outcome: coronary and vascular events, stroke, mortality, cognition and cancer follow-up

Released conclusion: Evidence is clearer after vascular disease than for starting primary prevention after age 75, and it does not establish longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02099123 · NCT04262206

Identifier and correction state checked · projected from sixth-coverage-edition.json

primary-randomized-report · peer-reviewed

LiFE randomized trial

PMID 22872695

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-randomized-report
Study designRandomized trialprimary randomized report
Population or modelPeopleSmall three-arm randomized trial with self-reported fall-rate outcomes
Population/model
LiFE selected high-risk home-living population and measured fall outcomes
Intervention and comparator
Lifestyle integrated Functional Exercise (LiFE); three-arm randomized parallel trial with fall calendars over 12 months; structured exercise and sham gentle exercise
Duration
Not separately structured in this publication record
Measured outcome
self-reported fall rate

What the covered evidence found

317 selected ambulatory home-living adults; three home-based groups · Fall rate 1.66 versus 2.28; IRR 0.69 · Structured exercise versus control IRR 0.81 was not significant · Balance and function secondary measures differed

What it does not establish

Institutionalized or general population · Fracture, disability, healthspan or lifespan · Cross-program ranking · Unsupervised instruction or injury guarantee

Limitations: Small selected sample · Self-reported falls · Limited power · Multiple outcomes and self-report

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none-linked-as-of-2026-08-26

Connected reporting

LiFE reduced self-reported falls by embedding activity in daily routines

Measured outcome: self-reported fall rate

Released conclusion: Fall rates were 1.66, 1.90 and 2.28 per person-year; LiFE versus control IRR 0.69 (95% CI 0.48–0.99).

Boundary: The trial did not establish fewer fractures, disability, longer healthspan or lifespan, and it does not test unsupervised use in other populations.

Applicable registry records: ACTRN12606000025538

Identifier and correction state checked · projected from eighteenth-coverage-claim-map.json

peer-reviewed-protocol · peer-reviewed

Finger Protocol

PMID 23332672

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-protocol
Study designRandomized trialrandomized trial protocol
Population or modelPeoplerandomized human cognitive-test evidence for a combined two-year multidomain program
Population/model
Finnish adults age 60–77 selected through CAIDE risk and cognitive screening
Intervention and comparator
FINGER; randomized multidomain trial
Duration
Not separately structured in this publication record
Measured outcome
multidomain intervention definition and prespecified cognitive endpoints

What the covered evidence found

FINGER delivered diet guidance, exercise, cognitive and social activity, and vascular-risk monitoring together.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The design cannot assign the observed difference to any one component.

Funding and conflicts: Public and nonprofit research funding; the primary report lists investigator disclosures and does not establish an intervention-component sponsor effect.

Correction/retraction state: none

Connected reporting

FINGER slightly improved cognitive-test scores. It did not prove dementia prevention

Measured outcome: global cognitive composite and domain tests

Released conclusion: A combined two-year program produced a small cognitive-test advantage; it cannot identify a winning component or establish dementia, disability, mortality, healthspan, or lifespan benefit.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01041989

Identifier and correction state checked · projected from eighth-coverage-edition.json

primary-randomized-report · peer-reviewed

Look AHEAD cardiovascular outcomes

PMID 23796131

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-randomized-report
Study designRandomized trialprimary randomized report
Population or modelPeopleLarge randomized cardiovascular-outcome trial stopped for futility
Population/model
Adults age 45–75 with type 2 diabetes and overweight or obesity who could complete an exercise test
Intervention and comparator
Structured intensive lifestyle versus diabetes support and education
Duration
Median 9.6 years
Measured outcome
Cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for angina

What the covered evidence found

The primary cardiovascular composite occurred in 403 intensive-lifestyle and 418 support/education participants; hazard ratio 0.95, P=0.51.

What it does not establish

No statistically significant cardiovascular-event reduction

Limitations: Stopped for futility, evolving medical care and narrowing weight contrast

Funding and conflicts: NIH/HHS and listed institutional/corporate support; corporate supporters reportedly had no design, analysis or reporting role; disclosures linked.

Correction/retraction state: corrected-by-NEJMx140022

Connected reporting

Look AHEAD improved weight and risk factors—not cardiovascular event rates

Measured outcome: major cardiovascular events, weight and cardiometabolic risk factors

Released conclusion: The primary cardiovascular outcome occurred in 403 intensive-lifestyle participants and 418 controls (hazard ratio 0.95; P=0.51). Weight loss and several risk factors improved more with intensive lifestyle.

Boundary: Look AHEAD did not establish that its intensive lifestyle program reduced major cardiovascular events or extended life in this population.

Applicable registry records: NCT00017953

Identifier and correction state checked · projected from seventeenth-coverage-claim-map.json

peer-reviewed-follow-up · peer-reviewed

Prosper Follow Up

PMID 24023757

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-follow-up
Study designRandomized trialpost trial follow up
Population or modelPeoplerandomized human trials, subgroup analyses, extended follow-up, and individual-participant meta-analysis
Population/model
PROSPER participants linked to long-term outcomes
Intervention and comparator
statins; trials and pooled evidence
Duration
Not separately structured in this publication record
Measured outcome
mortality, vascular outcomes, and cancer

What the covered evidence found

The featured statin evidence did not establish better cognition, less disability, all-cause survival, or longer human lifespan, and two dedicated older-adult trials had no posted results.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: Absence of posted results is not evidence of no effect; the trial registries are context only.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Statin evidence changes with age, risk and prevention setting

Measured outcome: coronary and vascular events, stroke, mortality, cognition and cancer follow-up

Released conclusion: Evidence is clearer after vascular disease than for starting primary prevention after age 75, and it does not establish longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02099123 · NCT04262206

Identifier and correction state checked · projected from sixth-coverage-edition.json

peer-reviewed-primary · peer-reviewed

Olesen Resveratrol Exercise

PMID 24514907

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-primary
Study designRandomized trialrandomized exercise trial
Population or modelPeoplesmall randomized human trials dominated by cognitive tests and metabolic or cardiovascular surrogate endpoints
Population/model
older men undertaking exercise training
Intervention and comparator
resveratrol; small heterogeneous trials
Duration
Not separately structured in this publication record
Measured outcome
skeletal-muscle metabolic and cardiovascular training adaptations

What the covered evidence found

Resveratrol did not add metabolic benefit and may blunt some exercise-training adaptations in older men.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: A small trial cannot establish universal harm or predict an individual's response.

Funding and conflicts: Mixed investigator, public, and public-private support; some study products were manufacturer supplied.

Correction/retraction state: none

Connected reporting

Resveratrol has a longevity reputation. Human trials tell a mixed story

Measured outcome: memory tests, metabolic markers, body composition, inflammation and exercise adaptation

Released conclusion: One small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01150955 · NCT01364961 · NCT01412645

Identifier and correction state checked · projected from seventh-coverage-edition.json

primary-randomized-follow-up · peer-reviewed

DPPOS 15-year diabetes and microvascular outcomes

PMID 26377054

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-randomized-follow-up
Study designRandomized trialprimary randomized follow up
Population or modelPeopleLong randomized follow-up with diabetes incidence benefit and an overall null aggregate microvascular comparison
Population/model
Adults with impaired glucose tolerance and BMI at least 24 kg/m² in the original DPP cohort
Intervention and comparator
Intensive lifestyle or metformin versus placebo · Original randomized groups · Subgroup/exposure-defined comparisons
Duration
Mean 15-year follow-up · 15-year follow-up · 15-year follow-up
Measured outcome
Diabetes incidence; Aggregate retinopathy, nephropathy and neuropathy prevalence; Aggregate microvascular prevalence

What the covered evidence found

At 15 years, cumulative diabetes incidence was 55% with lifestyle, 56% with metformin and 62% with placebo; hazard ratios were 0.73 and 0.82 versus placebo. · Overall aggregate microvascular prevalence did not differ significantly by original randomized group: 11.3% lifestyle, 13.0% metformin and 12.4% placebo. · Women-only differences and the lower prevalence among participants who did not develop diabetes are secondary subgroup or exposure-defined findings.

What it does not establish

No demonstrated cardiovascular, mortality, healthspan or lifespan benefit · No overall randomized microvascular benefit · No whole-cohort randomized microvascular effect

Limitations: Post-DPP lifestyle exposure across groups, unmasked follow-up treatment and diminishing separation · End-study prevalence composite and shared lifestyle exposure · Multiplicity, subgroup scope and nonrandomized diabetes-status comparison

Funding and conflicts: NIDDK/NIH support; governing paper declares no conflicts.

Correction/retraction state: none-linked-as-of-2026-08-26

Connected reporting

DPP prevention effects persisted for 15 years—without an overall microvascular difference

Measured outcome: cumulative type 2 diabetes incidence and aggregate microvascular disease

Released conclusion: Over 15 years, cumulative diabetes incidence was 55% with intensive lifestyle, 56% with metformin and 62% with placebo. The randomized groups did not differ significantly in aggregate microvascular prevalence.

Boundary: The follow-up did not demonstrate that either randomized assignment reduced the aggregate microvascular outcome or extended life.

Applicable registry records: NCT00004992 · NCT00038727

Identifier and correction state checked · projected from seventeenth-coverage-claim-map.json

peer-reviewed-secondary · peer-reviewed

Allhat Llt Older

PMID 28531241

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-secondary
Study designRandomized trialrandomized trial secondary analysis
Population or modelPeoplerandomized human trials, subgroup analyses, extended follow-up, and individual-participant meta-analysis
Population/model
Adults aged 65 and older without baseline atherosclerotic cardiovascular disease
Intervention and comparator
statins; trials and pooled evidence
Duration
Not separately structured in this publication record
Measured outcome
all-cause mortality and coronary events

What the covered evidence found

PROSPER's primary-prevention subgroup and ALLHAT-LLT's older-adult analysis were neutral, while pooled evidence is clearer for older adults with established vascular disease.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: ALLHAT-LLT had crossover and modest LDL separation; subgroup and meta-analytic evidence do not replace an adequately powered dedicated trial.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

Statin evidence changes with age, risk and prevention setting

Measured outcome: coronary and vascular events, stroke, mortality, cognition and cancer follow-up

Released conclusion: Evidence is clearer after vascular disease than for starting primary prevention after age 75, and it does not establish longer life.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT02099123 · NCT04262206

Identifier and correction state checked · projected from sixth-coverage-edition.json

primary-randomized-report · peer-reviewed

TJQMBB six-month randomized trial

PMID 30208396

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedprimary-randomized-report
Study designRandomized trialprimary randomized report
Population or modelPeopleThree-arm randomized trial with active comparators and separate follow-up evidence
Population/model
TJQMBB selected community population and measured fall outcomes
Intervention and comparator
therapeutically tailored Tai Ji Quan (TJQMBB); single-blind three-arm randomized clinical trial; multimodal exercise and stretching
Duration
Not separately structured in this publication record
Measured outcome
incidence of falls during the six-month intervention

What the covered evidence found

670 selected adults; tailored TJQMBB versus multimodal versus stretching · 152 versus 363 falls; IRR 0.42 versus stretching · IRR 0.69 versus multimodal exercise · Injurious-fall paper is separate follow-up

What it does not establish

Generic tai chi or other settings · Lifespan or guaranteed injury prevention · Universal superiority · Individual recommendation

Limitations: 24 weeks and active comparators · Falls during intervention · Selected sample and delivery · Later analysis and representativeness

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none-linked-as-of-2026-08-26

Connected reporting

A tailored Tai Ji Quan program reduced falls in one high-risk trial

Measured outcome: incidence of falls during the six-month intervention

Released conclusion: Falls numbered 152, 218 and 363; TJQMBB versus stretching IRR 0.42 (95% CI 0.31–0.56) and versus multimodal exercise 0.69 (0.52–0.94).

Boundary: The trial did not test every tai chi class, institutionalized or broadly frail populations, permanent independence, healthspan or lifespan.

Applicable registry records: NCT02287740

Identifier and correction state checked · projected from eighteenth-coverage-claim-map.json

peer-reviewed-counterevidence · peer-reviewed

Nr Mci

PMID 37994989

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-counterevidence
Study designRandomized trialrandomized trial
Population or modelPeopleMaturity described in linked reporting
Population/model
20 adults with mild cognitive impairment
Intervention and comparator
See linked reporting
Duration
Not separately structured in this publication record
Measured outcome
NAD signal and cognition

What the covered evidence found

Featured NR trials did not show broad metabolic, mitochondrial, motor, or cognitive benefit.

What it does not establish

This record is not a recommendation or proof of longer life.

Limitations: Trials were small, short and heterogeneous.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

NAD precursors raise some metabolites; human longevity benefits remain unproven

Measured outcome: metabolites, physiology and short-term function

Released conclusion: Small trials show target engagement, not broad clinical, healthspan or lifespan benefit—and products and routes are not interchangeable.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Identifier and correction state checked · projected from fourth-coverage-edition.json

peer-reviewed-follow-up · peer-reviewed

Sprint Extended Cognition

PMID 39819096

Publication identity and source facts are kept separate from the linked story’s interpretation.

Publication statepeer-reviewedpeer-reviewed-follow-up
Study designRandomized trialobservational post trial follow up
Population or modelPeoplelarge randomized human cardiovascular-outcomes evidence with secondary and post-trial cognitive follow-up
Population/model
surviving SPRINT participants after the randomized treatment period
Intervention and comparator
blood pressure; large randomized trial
Duration
Not separately structured in this publication record
Measured outcome
later cognitive outcomes

What the covered evidence found

SPRINT MIND did not significantly reduce probable dementia; its favorable mild-cognitive-impairment result was secondary and SPRINT did not test biological aging or lifespan.

What it does not establish

The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Limitations: The later cognitive report followed participants observationally after the randomized treatment period.

Funding and conflicts: Funding and conflict context is retained in linked reporting; this source record does not separately structure it.

Correction/retraction state: none

Connected reporting

SPRINT reduced cardiovascular events—not aging itself

Measured outcome: cardiovascular events, mortality, adverse events and cognitive outcomes

Released conclusion: Intensive treatment lowered cardiovascular events and mortality in eligible high-risk adults, with more hypotension, electrolyte problems and kidney injury.

Boundary: The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.

Applicable registry records: NCT01206062

Identifier and correction state checked · projected from sixth-coverage-edition.json

Method and limits

One canonical publication identity, once.

Records are deduplicated by DOI, PMID, PMCID or another verified canonical source from the governed evidence sets behind released reporting. Primary publications and governing syntheses are included; registries, labels and guidance remain separate source types. Unknown correction, duration or funding fields stay explicit rather than being inferred.