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Population / model
Current trial-reporting guidance illustrated with a four-week pectin pilot and the long-running ACTIVE cognitive-training trial
Design / record
Mixed or synthesized evidence · methods synthesis with two bounded randomized-trial examples
Measured outcome
how primary, secondary, exploratory and subgroup results map to prespecified questions, analysis populations and uncertainty
Released bottom lineOutcome labels are a map of the trial's questions, not a truth score; multiplicity, interaction tests, analysis populations, effect size, uncertainty and replication remain separate checks.
Evidence boundaryThe explainer does not establish that pectin or cognitive training improves health, prevents dementia, extends life or merits a treatment recommendation.
In selected healthy Japanese adults age 65 or older, high-dose NMN produced a large biochemical change. The registered hearing outcome and measured physical function did not improve.
Population / model
62 selected healthy Japanese adults age 65 or older randomized at one center; 60 entered the authors' efficacy analysis and 58 completed 24 weeks
Design / record
Small randomized trial · double-blind randomized trial; 1,250 mg/day oral NMN versus matched placebo for 24 weeks
Measured outcome
whole-blood NAD target engagement, registered four-frequency hearing change and measured physical function
Released bottom lineWhole-blood NAD rose markedly, while the registered hearing outcome and measured physical function did not show attributable improvement.
Evidence boundaryThe trial did not establish slower aging, tissue rejuvenation, disease prevention, healthspan or lifespan benefit, long-term safety or a supplement recommendation.
Physical features, accumulated deficits and performance tasks measure different inputs. Learn what a changed frailty score can and cannot establish.
Population / model
Three separate historical older-adult cohorts: Fried 5,317 aged 65+; Searle 754 aged 70+ with 681 at follow-up; Guralnik 5,174 selected home-living respondents aged 71+ with task-specific denominators. No pooling.
Design / record
Observational study · Methods explainer comparing physical phenotype, deficit accumulation and performance inputs; no intervention comparison or score conversion
Measured outcome
Instrument-specific physical components, selected health deficits and performance tasks; observational prognostic associations
Released bottom lineThe instruments use different inputs and protocols. These core observational validations do not by themselves establish that treatment-induced score changes extend lifespan.
Evidence boundaryNo individual diagnosis, best-tool ranking, score conversion, treatment recommendation or proof that a changed score reverses aging or adds healthy years.
In 31 older adults with frailty or pre-frailty, low-methoxy pectin did not change the inflammatory outcomes the paper defined as primary. Secondary and exploratory signals remain preliminary.
Population / model
31 adults older than 65 with frailty or pre-frailty randomized at one Nottingham centre; 29 completed; most were pre-frail
Design / record
Small randomized trial · blinded parallel randomized pilot; 10 g/day low-methoxy citrus pectin plus whey/cocoa versus matched whey/cocoa without pectin for four weeks
Measured outcome
paper-defined inflammatory markers plus secondary physical-function and psychological measures
Released bottom lineThe paper-defined TNF-α, IFN-γ and zonulin outcomes showed no significant between-group change; secondary physical, psychological and exploratory microbiome signals require replication.
Evidence boundaryThe pilot did not establish treatment or reversal of frailty, a causal microbiome mechanism, broad safety, durable function, disease prevention, healthspan, lifespan or supplement advice.
A four-week crossover trial found no detectable average increase in fasting immune-cell autophagic flux. It did not test other tissues, older adults, healthspan or lifespan.
Population / model
74 healthy adults age 20–50 randomized; 63 completed both periods and 61 entered the adjusted primary analysis
Design / record
Small randomized trial · single-blind randomized crossover; 10% versus 20% protein energy for 4 weeks each at calculated energy balance
Measured outcome
fasting autophagic flux in circulating immune cells
Released bottom lineA 4-week diet providing 10% rather than 20% of energy from protein did not produce a detectable average increase in fasting PBMC autophagic flux.
Evidence boundaryThe trial did not establish no effect in other cell types or tissues, a long-term safety profile, a healthspan or lifespan effect, or dietary advice.
Fifteen randomized studies measured intrinsic capacity, quality of life or other multidimensional scores. Their results could be described study by study—not combined into extra healthy years or a treatment ranking.
Population / model
4,656 participants across 15 unique randomized studies, mostly older adults in high- or upper-middle-income settings
Design / record
Mixed or synthesized evidence · registered systematic review with qualitative synthesis; study-specific randomized comparators
Measured outcome
intrinsic capacity, quality of life and other multidimensional function or well-being scores
Released bottom lineThe review described small, heterogeneous study-level signals but produced no pooled effect estimate or evidence of added healthy years.
Evidence boundaryThe review did not establish a treatment ranking, benefit from every exercise program, class-wide supplement or caloric-restriction benefit, disease prevention, mortality benefit or lifespan extension.
A later analysis combined five very different first events. Aspirin and placebo rates were nearly identical—but the way the endpoint was built matters as much as the result.
Population / model
19,114 generally healthy community-dwelling older adults in Australia and the United States
Design / record
Large randomized trial · secondary intention-to-treat analysis of randomized aspirin versus placebo assignment over median 4.7 years
Measured outcome
time to first cardiovascular disease, diabetes, dementia, cancer or death event
Released bottom lineAspirin and placebo rates were 82.1 and 82.7 events per 1,000 person-years; HR 0.98, 95% CI 0.92–1.05.
Evidence boundaryThe analysis did not prove zero effect, isolate component effects, validate a universal healthspan measure or establish advice for an individual.
The models exposed sex-dependent patterns across organs and health outcomes. They did not become clinical tests, individual forecasts or evidence that aging was slowed.
Population / model
Sex-stratified MRI, proteomic and metabolomic models using MULTI cohorts, with downstream UK Biobank, BLSA, ADNI and A4 analyses
Design / record
Observational study · age-prediction model development and internal holdouts, followed by observational, genetic and secondary trial-data analyses
Measured outcome
chronological-age prediction, biological age gaps, incident disease, mortality and cognitive trajectories
Released bottom lineSex-stratified models exposed different patterns, but mixed performance and absent external validation keep them research tools rather than clinical tests.
Evidence boundaryThe study did not establish diagnosis, individual prognosis, a validated surrogate endpoint, treatment response, slower aging, healthspan or lifespan.
A 25% relative change can mean five percentage points or one. This guide shows how baseline risk, denominator, follow-up and uncertainty set the scale.
Population / model
SPRINT’s 9,361 higher-risk adults without diabetes or prior stroke and ASPREE’s 19,114 selected older primary-prevention adults
Design / record
Mixed or synthesized evidence · methods explainer using two large randomized trials; outcomes and scales kept separate
Measured outcome
cardiovascular composites, mortality, major hemorrhage and reported effect measures
Released bottom lineRelative and absolute effects answer different questions; both require the two group rates, denominator, outcome, follow-up and uncertainty.
Evidence boundaryThe explainer does not estimate an individual’s risk, rank treatments, convert hazard ratios into cumulative risk, or recommend a medication or blood-pressure target.
The model was associated with prevalent and incident disease and added little discrimination beyond chronological age; it is not a reason to obtain CT imaging.
Population / model
7,837 adults from one University of Tokyo health-screening cohort, including 3,174 initially disease-free people followed a median 6.5 years
Design / record
Observational study · same-source model development, prevalent-disease testing and longitudinal observational testing; CT age gap compared with chronological age
Measured outcome
chronological-age prediction, prevalent disease, incident disease and discrimination
Released bottom lineEach 1-SD higher CT age gap was associated with prevalent disease (OR 1.35) and incident disease (HR 1.24); five-year tAUC was 0.700 versus 0.688 for chronological age.
Evidence boundaryThe study did not establish causation, external validity, clinical utility, diagnosis, prevention benefit, slower aging or a reason to obtain CT imaging.
Six proteomic clocks shifted in a 42-person ancillary analysis, but the result does not establish slower aging, healthspan, lifespan or benefit in healthy people.
Population / model
42 adults with idiopathic pulmonary fibrosis who consented and had complete four-timepoint serum samples from a 71-person randomized phase 2a trial
Design / record
Early human study · exploratory ancillary analysis across three rentosertib regimens and placebo over 12 weeks
Measured outcome
predicted-age change from six protein-based aging clocks
Released bottom lineTwenty-one of 54 regimen–time–clock comparisons met the authors’ Q<0.10 threshold, concentrated at week 4.
Evidence boundaryThe analysis did not establish clinical benefit, slower aging, healthspan, lifespan, healthy-person benefit or a validated surrogate endpoint.
Two large observational analyses found substantially higher mortality with current cigarette smoking and lower excess mortality after stopping. The estimates describe populations; they do not promise a particular person extra years.
Population / model
1.48 million adults age 20–79 in four national cohorts, with a separate 202,248-person US linked-cohort analysis
Design / record
Observational study · observational current and former cigarette smokers compared with never smokers; cessation timing compared with continued smoking
Measured outcome
all-cause and cause-specific mortality plus modeled survival
Released bottom lineCurrent cigarette smoking was associated with roughly three times the mortality of never smoking; stopping was associated with lower excess mortality at every age studied.
Evidence boundaryThe analyses did not establish an exact causal effect for every subgroup, forecast an individual lifespan, or compare cessation treatments.
In 670 selected community-dwelling older adults at high risk of falling, a therapeutically tailored Tai Ji Quan program reduced falls over 24 weeks versus stretching and multimodal exercise.
Population / model
670 community-dwelling adults age 70 years or older with a prior fall or impaired mobility
Design / record
Large randomized trial · single-blind three-arm randomized clinical trial; multimodal exercise and stretching
Measured outcome
incidence of falls during the six-month intervention
Released bottom lineFalls 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).
Evidence boundaryThe trial did not test every tai chi class, institutionalized or broadly frail populations, permanent independence, healthspan or lifespan.
In 10,251 adults with type 2 diabetes and high cardiovascular risk, an intensive multi-drug strategy targeting near-normal glycated hemoglobin did not significantly reduce the primary cardiovascular outcome and increased all-cause mortality.
Population / model
10,251 adults with established type 2 diabetes and high cardiovascular risk
Design / record
Large randomized trial · intensive glycemia target below 6% versus standard target of 7.0% to 7.9%
Measured outcome
major cardiovascular events, all-cause mortality and treatment harms
Released bottom lineThe 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.
Evidence boundaryACCORD does not show that all glucose lowering is harmful; it tested one intensive, multi-drug target strategy in a high-risk population.
Among adults at high risk for type 2 diabetes, the DPP lifestyle and metformin groups still had lower cumulative diabetes incidence after 15 years. The randomized groups did not differ significantly in the study’s aggregate microvascular outcome.
Population / model
2,776 surviving DPP participants with elevated glucose and overweight or obesity who joined long-term follow-up
Design / record
Large randomized trial · randomized lifestyle or metformin versus placebo, followed observationally after the original trial
Measured outcome
cumulative type 2 diabetes incidence and aggregate microvascular disease
Released bottom lineOver 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.
Evidence boundaryThe follow-up did not demonstrate that either randomized assignment reduced the aggregate microvascular outcome or extended life.
Among 317 selected older adults at high risk of falls, the LiFE program integrated balance and strength activities into everyday routines and reduced the self-reported fall rate versus sham gentle exercise over 12 months.
Population / model
317 ambulatory community-living adults age 70 years or older with recurrent or injurious falls
Design / record
Randomized trial · three-arm randomized parallel trial with fall calendars over 12 months; structured exercise and sham gentle exercise
Measured outcome
self-reported fall rate
Released bottom lineFall rates were 1.66, 1.90 and 2.28 per person-year; LiFE versus control IRR 0.69 (95% CI 0.48–0.99).
Evidence boundaryThe trial did not establish fewer fractures, disability, longer healthspan or lifespan, and it does not test unsupervised use in other populations.
In 5,145 adults with type 2 diabetes and overweight or obesity, intensive lifestyle intervention produced greater sustained weight loss and improved several risk factors. It did not significantly reduce the trial’s primary cardiovascular outcome.
Population / model
5,145 adults age 45–75 with type 2 diabetes and overweight or obesity
Design / record
Large randomized trial · intensive lifestyle intervention versus diabetes support and education
Measured outcome
major cardiovascular events, weight and cardiometabolic risk factors
Released bottom lineThe 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.
Evidence boundaryLook AHEAD did not establish that its intensive lifestyle program reduced major cardiovascular events or extended life in this population.
In 5,451 older adults at increased fall-injury risk, a nurse-led multifactorial strategy did not significantly reduce the first adjudicated serious fall injury versus enhanced usual care. A secondary self-reported fall-injury outcome differed.
Population / model
5,451 community-dwelling primary-care patients age 70 years or older at increased risk for serious fall injuries
Design / record
Large randomized trial · pragmatic cluster-randomized trial across 86 primary-care practices; enhanced usual care with falls-prevention information
Measured outcome
time to first adjudicated serious fall injury
Released bottom lineFirst 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.
Evidence boundaryThe trial did not establish a significant primary-outcome reduction, equivalence, longer independence, healthspan or lifespan.
In NordICC, inviting adults to one colonoscopy reduced colorectal-cancer incidence at 13 years. Colorectal-cancer mortality was not significantly lower, and participation limits what the invitation result says about completing screening.
Population / model
Adults age 55–64 in Norway, Poland and Sweden
Design / record
Randomized trial · randomized invitation versus usual care
Measured outcome
colorectal-cancer incidence and mortality
Released bottom lineAt 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.
Evidence boundaryA colorectal-cancer mortality or all-cause survival benefit was not demonstrated.
NLST found fewer lung-cancer deaths with three annual low-dose CT screens than with chest radiography in selected current and former heavy smokers. The benefit came with many positive results that were false positives under the trial definition.
Population / model
Selected current and former heavy smokers age 55–74
Design / record
Randomized trial · randomized low-dose CT versus chest radiography
Measured outcome
lung-cancer and all-cause mortality
Released bottom lineThe 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.
Evidence boundaryBenefit for never-smokers, average-risk adults or overall lifespan.
After 21 years in Rotterdam’s ERSPC section, repeated PSA-based screening reduced prostate-cancer mortality and metastatic disease in the primary age group, while producing substantially more prostate-cancer diagnoses.
Population / model
Men age 55–74 in Rotterdam; primary group age 55–69
Design / record
Randomized trial · randomized screening invitation versus usual care
Measured outcome
prostate-cancer mortality, metastasis and diagnoses
Released bottom lineIn 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.
Evidence boundaryAn all-cause survival benefit or favorable balance for every individual.
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.
Population / model
Very small sample of older adults
Design / record
Small randomized trial · very small randomized trial
Measured outcome
biomarkers and physical function
Released bottom lineA 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.
Evidence boundaryGlyNAC’s small trial cannot establish reversal of aging
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.
Population / model
Older adults with subjective cognitive decline
Design / record
Small randomized trial · small randomized phase 2b trial
Measured outcome
memory and cognitive tests
Released bottom lineIn 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.
Evidence boundarySpermidine did not improve the trial’s primary memory outcome
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.
Population / model
Selected older adults with lower mitochondrial function
Design / record
Small randomized trial · small randomized trial
Measured outcome
walking distance, muscle endurance and ATP production
Released bottom lineENERGIZE 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.
Evidence boundaryUrolithin A missed both primary outcomes in older adults
In selected older adults without cardiovascular disease, low-dose aspirin did not significantly reduce the trial’s cardiovascular composite. Major hemorrhage occurred more often.
Population / model
19,114 community-dwelling older adults without cardiovascular disease at enrollment
Design / record
Large randomized trial · large randomized trial
Measured outcome
cardiovascular events · major bleeding
Released bottom lineIn selected older adults without cardiovascular disease, low-dose aspirin did not significantly reduce the trial’s cardiovascular composite. Major hemorrhage occurred more often.
Evidence boundaryASPREE did not lower cardiovascular events—and increased major bleeding
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.
Population / model
19,114 community-dwelling older adults without cardiovascular disease, dementia or independence-limiting disability at enrollment
Design / record
Large randomized trial · large randomized trial
Measured outcome
disability-free survival · major bleeding
Released bottom lineIn 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.
Evidence boundaryASPREE found no gain in disability-free survival—and more major bleeding
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.
Population / model
19,114 original ASPREE participants; 14,907 cancer-free survivors in the post-trial analysis
Design / record
Randomized trial · randomized trial plus observational extension
Measured outcome
cancer mortality · long-term follow-up
Released bottom lineThe 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.
Evidence boundaryASPREE’s cancer signal changed across longer follow-up
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.
Population / model
Very small selected sample of young healthy men
Design / record
Observational study · cross-sectional swimmer versus matched comparison group
Measured outcome
brown-fat activity and thermogenesis
Released bottom lineA 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.
Evidence boundaryCold-water studies measure thermogenesis—not longer life
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.
Population / model
Small selected group of healthy adults age 64 or older
Design / record
Other human evidence · single-arm pre/post study without a control
Measured outcome
selected blood-cell telomere and senescence markers
Released bottom lineA 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.
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.
Population / model
Middle-aged Finnish men
Design / record
Observational study · prospective cohort by self-reported frequency
Measured outcome
cardiovascular and all-cause mortality association
Released bottom lineOne 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.
Evidence boundarySauna use was associated with lower mortality—not proven to extend life
Clinical fractures were more frequent with testosterone than placebo in TRAVERSE; a smaller substudy’s bone-density gain cannot substitute for fracture outcomes.
Population / model
5,204 TRAVERSE participants: middle-aged and older men with symptoms, repeatedly low testosterone and preexisting or high cardiovascular risk
Design / record
Randomized trial · randomized trials
Measured outcome
clinical fractures and bone-density measures
Released bottom lineClinical fractures were more frequent with testosterone than placebo in TRAVERSE; a smaller substudy’s bone-density gain cannot substitute for fracture outcomes.
Evidence boundaryTestosterone did not prevent fractures in TRAVERSE
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.
Population / model
790 symptomatic men age 65 or older with repeatedly low testosterone; 390 enrolled in the Physical Function Trial
Design / record
Randomized trial · one-year randomized trials
Measured outcome
six-minute walking distance and a 50-meter improvement threshold
Released bottom lineThe prespecified Physical Function Trial threshold was not significant in its enrolled subgroup; broader secondary walking results do not establish disability prevention, healthspan or longevity.
Evidence boundaryTestosterone’s walking result was modest—not an anti-aging effect
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.
Population / model
5,246 men age 45–80 with symptoms, repeatedly low testosterone and preexisting or high cardiovascular risk
Design / record
Large randomized trial · large randomized noninferiority trial
Measured outcome
major cardiovascular events and cardiovascular safety outcomes
Released bottom lineAmong 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.
Evidence boundaryTRAVERSE found cardiovascular noninferiority—not a longevity benefit
Two randomized trials support meaningful sleep improvement in older adults; they did not test dementia prevention, biological aging or lifespan.
Population / model
46 adults in one insomnia trial and 123 older adults in a separate late-life trial
Design / record
Randomized trial · randomized behavioral trials
Measured outcome
sleep latency, sleep efficiency, insomnia remission and durability
Released bottom lineTwo randomized trials support meaningful sleep improvement in older adults; they did not test dementia prevention, biological aging or lifespan.
ACTIVE supports trained-ability gains and some function signals, found no mortality benefit, and leaves a claims-based dementia subgroup methodologically disputed.
Population / model
2,832 independent U.S. adults age 65–94
Design / record
Randomized trial · randomized trial plus disputed secondary analysis
Measured outcome
trained abilities, daily function, all-cause mortality and claims-diagnosed dementia
Released bottom lineACTIVE supports trained-ability gains and some function signals, found no mortality benefit, and leaves a claims-based dementia subgroup methodologically disputed.
Evidence boundaryCognitive training improved practiced skills—not survival or proven dementia prevention
SAVE and ISAACC did not significantly reduce their primary cardiovascular outcomes; SAVE separately found symptom and quality-of-life benefits.
Population / model
2,717 adults with sleep apnea and cardiovascular or cerebrovascular disease; 1,264 non-sleepy adults after acute coronary syndrome
Design / record
Large randomized trial · large randomized trials
Measured outcome
major cardiovascular events, sleepiness, symptoms and quality of life
Released bottom lineSAVE and ISAACC did not significantly reduce their primary cardiovascular outcomes; SAVE separately found symptom and quality-of-life benefits.
Evidence boundaryCPAP improved symptoms—not cardiovascular events in major trials
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.
Population / model
1,260 Finnish adults age 60–77 at elevated dementia risk and with average-to-lower cognitive performance
Design / record
Randomized trial · randomized multidomain trial
Measured outcome
global cognitive composite and domain tests
Released bottom lineA 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.
Evidence boundaryFINGER slightly improved cognitive-test scores. It did not prove dementia prevention
LIFTMOR found BMD and function gains in a small, screened, closely supervised trial—not fracture prevention or proof that unsupervised heavy training is safe.
Population / model
101 screened postmenopausal women with low bone mass; mean age 65
Design / record
Small randomized trial · small supervised randomized trial
Measured outcome
bone density, strength and functional measures
Released bottom lineLIFTMOR found BMD and function gains in a small, screened, closely supervised trial—not fracture prevention or proof that unsupervised heavy training is safe.
Evidence boundaryLIFTMOR improved bone density in a small supervised trial—not fracture prevention
sleep latency, sleep quality and morning alertness
Released bottom lineSpecific prolonged-release melatonin trials reported modest sleep benefits; they did not test biological-age reversal, healthspan or lifespan.
Evidence boundaryMelatonin can shift sleep outcomes—not human aging
WHI found a formulation-specific mix of benefits and harms, no overall 18-year mortality difference, and no basis for general longevity prevention.
Population / model
Postmenopausal women age 50–79, separated by uterus status and hormone regimen
Design / record
Randomized trial · randomized trials
Measured outcome
disease events, breast cancer and all-cause mortality
Released bottom lineWHI found a formulation-specific mix of benefits and harms, no overall 18-year mortality difference, and no basis for general longevity prevention.
Evidence boundaryMenopausal hormone therapy treats symptoms. WHI did not show a longevity benefit
Arexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.
Population / model
Adults age 60 or older across three separate pivotal vaccine trials
Design / record
Randomized trial · three randomized vaccine trials
Measured outcome
RSV lower-respiratory disease or illness, acute respiratory disease and safety
Released bottom lineArexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.
Evidence boundaryRSV vaccines reduce respiratory disease. Separate trials cannot rank them
Randomized trials established shingles prevention. Dementia findings come from observational and quasi-experimental studies and do not prove prevention.
Population / model
Adults age 50 or older in ZOE-50 plus older vaccine-eligible cohorts in two dementia analyses
Design / record
Randomized trial · randomized and non-randomized evidence
Measured outcome
herpes-zoster disease and recorded dementia diagnoses
Released bottom lineRandomized trials established shingles prevention. Dementia findings come from observational and quasi-experimental studies and do not prove prevention.
Both groups improved with counseling and calorie restriction; the between-group cognitive difference was not significant and MRI measures were similar.
Population / model
604 adults age 65 or older without cognitive impairment, with family dementia history, overweight and a suboptimal diet
Design / record
Randomized trial · randomized dietary trial
Measured outcome
global cognition and structural MRI measures
Released bottom lineBoth groups improved with counseling and calorie restriction; the between-group cognitive difference was not significant and MRI measures were similar.
Evidence boundaryThe MIND diet trial found no cognitive edge over its active control
HORIZON reduced vertebral and hip fractures in postmenopausal osteoporosis, with outcome-specific duration and safety limits—not evidence of slower aging.
Population / model
7,765 postmenopausal women with osteoporosis; mean age about 73
Design / record
Large randomized trial · large randomized trial
Measured outcome
vertebral, hip and nonvertebral fractures plus bone density
Released bottom lineHORIZON reduced vertebral and hip fractures in postmenopausal osteoporosis, with outcome-specific duration and safety limits—not evidence of slower aging.
Evidence boundaryZoledronic acid reduced fractures in osteoporosis—not aging itself
Two mixed EPA+DHA trials were neutral on primary outcomes; prescription icosapent ethyl benefited a defined high-risk population with safety and comparator limits.
Population / model
Primary-prevention adults, older adults after myocardial infarction and statin-treated high-risk adults with elevated triglycerides
cardiovascular composites and components, mortality, atrial fibrillation and bleeding
Released bottom lineTwo mixed EPA+DHA trials were neutral on primary outcomes; prescription icosapent ethyl benefited a defined high-risk population with safety and comparator limits.
Evidence boundary“Omega-3” is not one intervention—and the trial results do not transfer
The three-year trial was null across its full cohort. Signals in higher-risk groups need confirmation and do not establish dementia prevention.
Population / model
977 community-dwelling adults age 70–84 with untreated hearing loss
Design / record
Randomized trial · randomized trial with subgroup signals
Measured outcome
three-year standardized global-cognition change
Released bottom lineThe three-year trial was null across its full cohort. Signals in higher-risk groups need confirmation and do not establish dementia prevention.
Evidence boundaryHearing intervention did not slow cognitive decline across the full ACHIEVE trial
Different eating windows and comparators produced different weight and fat findings; none tested biological aging, healthspan or lifespan.
Population / model
Adults with overweight or obesity in three trials lasting 12–14 weeks
Design / record
Randomized trial · short randomized trials
Measured outcome
weight, body composition, visceral fat and cardiometabolic markers
Released bottom lineDifferent eating windows and comparators produced different weight and fat findings; none tested biological aging, healthspan or lifespan.
Evidence boundaryHuman time-restricted-eating trials show mixed short-term results—not slower aging
COSMOS found small cognitive-test differences and modest movement in two DNA-methylation clocks; neither establishes dementia prevention or longer life.
Population / model
Older adults in related telephone, web, clinic and blood-based COSMOS substudies
cognitive-test scores, word recall and DNA-methylation biomarkers
Released bottom lineCOSMOS found small cognitive-test differences and modest movement in two DNA-methylation clocks; neither establishes dementia prevention or longer life.
Evidence boundaryMultivitamins moved some tests and aging clocks. What does that mean?
One small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.
Population / model
Healthy overweight older adults, obese men, older exercising men and men with metabolic syndrome
Design / record
Other human evidence · small heterogeneous trials
Measured outcome
memory tests, metabolic markers, body composition, inflammation and exercise adaptation
Released bottom lineOne small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.
Evidence boundaryResveratrol has a longevity reputation. Human trials tell a mixed story
Intensive treatment lowered cardiovascular events and mortality in eligible high-risk adults, with more hypotension, electrolyte problems and kidney injury.
Population / model
9,361 adults age 50 or older at elevated cardiovascular risk, without diabetes or prior stroke
Design / record
Large randomized trial · large randomized trial
Measured outcome
cardiovascular events, mortality, adverse events and cognitive outcomes
Released bottom lineIntensive treatment lowered cardiovascular events and mortality in eligible high-risk adults, with more hypotension, electrolyte problems and kidney injury.
Evidence is clearer after vascular disease than for starting primary prevention after age 75, and it does not establish longer life.
Population / model
Adults age 70 or older across mixed primary- and secondary-prevention settings
Design / record
Other human evidence · trials and pooled evidence
Measured outcome
coronary and vascular events, stroke, mortality, cognition and cancer follow-up
Released bottom lineEvidence is clearer after vascular disease than for starting primary prevention after age 75, and it does not establish longer life.
Evidence boundaryStatin evidence changes with age, risk and prevention setting
In generally healthy adults, vitamin D3 did not significantly reduce invasive cancer, major cardiovascular events, or fractures; deficiency treatment is a different question.
Population / model
25,871 generally healthy U.S. adults not selected for vitamin D deficiency, low bone mass or osteoporosis
Design / record
Large randomized trial · large randomized prevention trial
Measured outcome
invasive cancer, major cardiovascular events and clinical fractures
Released bottom lineIn generally healthy adults, vitamin D3 did not significantly reduce invasive cancer, major cardiovascular events, or fractures; deficiency treatment is a different question.
Evidence boundaryVitamin D is essential. VITAL still found no broad prevention benefit
A randomized trial found selected cardiometabolic improvements, while aging-biomarker results were mixed and lifespan was not measured.
Population / model
218 healthy, non-obese adults age 21–51
Design / record
Randomized trial · randomized trial
Measured outcome
metabolism, cardiometabolic risk factors and DNA-methylation biomarkers
Released bottom lineA randomized trial found selected cardiometabolic improvements, while aging-biomarker results were mixed and lifespan was not measured.
Evidence boundaryCALERIE tested calorie restriction for two years—not human lifespan
Human trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence.
Population / model
Older adults across community, clinical and mobility-limited populations
Design / record
Randomized trial · mature randomized evidence
Measured outcome
mobility, function, frailty, falls and all-cause mortality
Released bottom lineHuman trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence.
Evidence boundaryExercise has strong evidence for function—not proof of slower biological aging
Small trials show target engagement, not broad clinical, healthspan or lifespan benefit—and products and routes are not interchangeable.
Population / model
Mostly middle-aged or older adults with differing health profiles
Design / record
Other human evidence · small trials
Measured outcome
metabolites, physiology and short-term function
Released bottom lineSmall trials show target engagement, not broad clinical, healthspan or lifespan benefit—and products and routes are not interchangeable.
Evidence boundaryNAD precursors raise some metabolites; human longevity benefits remain unproven
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.
Population / model
18 adults age 40–85 with glaucoma or recent non-arteritic anterior ischemic optic neuropathy (planned enrollment)
Design / record
Early human study · no results yet
Measured outcome
planned safety, dose-limiting toxicity, laboratory and eye measures; no posted results
Released bottom lineA 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.
Evidence boundaryPartial-reprogramming trial is testing eye-treatment safety—not human rejuvenation
The 48-week randomized trial reported a null primary outcome, exploratory signals and substantial limits on broader healthy-aging claims.
Population / model
129 adults age 50–85 enrolled; 114 completers included in the published analysis
Design / record
Small randomized trial · small randomized trial
Measured outcome
visceral fat, body composition, biomarkers, surveys and safety
Released bottom lineThe 48-week randomized trial reported a null primary outcome, exploratory signals and substantial limits on broader healthy-aging claims.
Evidence boundaryPEARL trial found no change in its main visceral-fat outcome
The corrected randomized analysis is promising for its composite endpoint, while allocation deviations and lifespan limits remain visible.
Population / model
7,447 adults age 55–80 in Spain at high cardiovascular risk, without cardiovascular disease at enrollment
Design / record
Randomized trial · corrected randomized trial
Measured outcome
myocardial infarction, stroke or cardiovascular death
Released bottom lineThe corrected randomized analysis is promising for its composite endpoint, while allocation deviations and lifespan limits remain visible.
Evidence boundaryPREDIMED found fewer cardiovascular events after a Mediterranean-style diet—with a correction history
Duration, regularity and fragmentation carry health signals, but the featured studies do not show that changing one metric extends lifespan.
Population / model
Adults and community-dwelling older adults in observational sleep cohorts
Design / record
Observational study · mostly observational evidence
Measured outcome
mortality and frailty associations
Released bottom lineDuration, regularity and fragmentation carry health signals, but the featured studies do not show that changing one metric extends lifespan.
Evidence boundarySleep patterns are linked to healthy aging—but most evidence is observational
LIFE supports a meaningful mobility outcome in vulnerable older adults, while lifespan and universal-program claims remain untested.
Population / model
Community-dwelling and hospitalized older adults, including mobility-limited participants
Design / record
Randomized trial · randomized trials
Measured outcome
mobility disability and discharge function
Released bottom lineLIFE supports a meaningful mobility outcome in vulnerable older adults, while lifespan and universal-program claims remain untested.
peer-reviewed small human randomized trial with a prespecified hearing endpoint and biochemical target-engagement measures
Population / model
62 selected healthy Japanese adults age 65 or older randomized; 60 in the authors' efficacy analysis and 58 completers
Design / record
Randomized trial · 1,250 mg/day oral NMN versus matched placebo
Measured outcome
four-frequency hearing change, whole-blood NAD and related metabolites, physical function and short-term adverse events
Publication state
Peer Reviewed Accepted Article
Governed resultWhole-blood NAD rose markedly; hearing change was +1.25 dB in each arm and measured physical function did not show attributable improvement.
Evidence boundaryThe trial did not establish slower aging, tissue rejuvenation, disease prevention, healthspan or lifespan benefit, long-term safety or a supplement recommendation.
short-term heterogeneous randomized human evidence; no long-term or lifespan evidence
Population / model
Adults in 15 randomized trials; 10 trials contributed to pooled safety analyses
Design / record
Evidence synthesis · oral NMN regimens versus control conditions across included trials
Measured outcome
short-term adverse events, liver enzymes and metabolic outcomes
Publication state
Peer Reviewed
Governed resultNo clear pooled short-term excess in adverse events or ALT/AST and no broad metabolic benefit; long-term and uncommon harms remain unresolved.
Evidence boundaryShort, small and heterogeneous trials do not establish long-term safety, clinical benefit, healthspan, lifespan or a supplement recommendation.
Other human evidence · No treatment comparison in this article; instrument inputs and definitions only
Measured outcome
Strength, muscle quantity/quality and performance roles in the consensus definition
Publication state
Peer Reviewed
Governed resultThe consensus distinguishes strength, quantity/quality confirmation and performance severity.
Evidence boundaryThese source-specific methods and observational associations do not by themselves establish that treatment-induced score changes extend lifespan; no diagnostic advice or cross-tool conversion.
Original observational analysis; not treatment-surrogate validation
Population / model
5,317 adults aged 65+; observational CHS analysis
Design / record
Observational study · No treatment comparison in this article; instrument inputs and definitions only
Measured outcome
Original physical components and subsequent prognostic associations
Publication state
Peer Reviewed
Governed resultFive physical components define this original phenotype; individual components retain protocol and evaluability requirements.
Evidence boundaryThese source-specific methods and observational associations do not by themselves establish that treatment-induced score changes extend lifespan; no diagnostic advice or cross-tool conversion.
Historical observational validation; not a treatment effect
Population / model
5,174 selected home-living personal respondents aged 71+; task denominators vary
Design / record
Observational study · No treatment comparison in this article; instrument inputs and definitions only
Measured outcome
Standing balance, eight-foot walk and five chair rises
Publication state
Peer Reviewed
Governed resultThree original domain scores range 0–4 and sum to 0–12; task-specific denominators vary.
Evidence boundaryThese source-specific methods and observational associations do not by themselves establish that treatment-induced score changes extend lifespan; no diagnostic advice or cross-tool conversion.
Historical cohort methodology; not an intervention trial
Population / model
754 community-dwelling non-disabled adults aged 70+; 681 at follow-up
Design / record
Observational study · No treatment comparison in this article; instrument inputs and definitions only
Measured outcome
Multisystem deficit construction and observational prediction
Publication state
Peer Reviewed
Governed resultSelected deficits are coded on a 0–1 scale; consistent items matter for serial individual comparisons.
Evidence boundaryThese source-specific methods and observational associations do not by themselves establish that treatment-induced score changes extend lifespan; no diagnostic advice or cross-tool conversion.
peer-reviewed small randomized pilot with retrospective registration and paper-versus-registry outcome-hierarchy discrepancies
Population / model
31 adults older than 65 with frailty or pre-frailty randomized at one Nottingham centre; 29 completed; most were pre-frail
Design / record
Randomized trial · 10 g/day low-methoxy citrus pectin plus 10 g whey and 10 g cocoa versus the same whey/cocoa without pectin
Measured outcome
paper-defined TNF-α, IFN-γ and zonulin changes; secondary physical-function and psychological measures; exploratory microbiome composition
Publication state
Peer Reviewed
Governed resultNo significant between-group change in paper-defined TNF-α, IFN-γ or zonulin outcomes; several secondary and exploratory signals favored pectin.
Evidence boundaryThe pilot did not establish treatment or reversal of frailty, a causal microbiome mechanism, broad safety, durable function, disease prevention, healthspan, lifespan or supplement advice.
peer-reviewed randomized crossover biomarker trial with a dynamic whole-blood autophagic-flux assay
Population / model
74 healthy adults age 20–50 randomized in Adelaide; 63 completed both diets and 61 entered the adjusted primary analysis
Design / record
Randomized trial · 10% versus 20% of energy from protein, prescribed at calculated energy balance
Measured outcome
fasting autophagic flux in circulating immune cells measured by LC3B-II turnover during lysosomal inhibition
Publication state
Peer Reviewed
Governed resultAdjusted reduced-minus-average protein difference −8.46 ng LC3B-II/mg protein/hour (95% CI −24.06 to 7.14; p=0.28; n=61).
Evidence boundaryThe result applies to fasting PBMC flux under this short energy-balanced diet contrast; it does not establish effects in other tissues, long-term safety, slower aging, healthspan, lifespan or dietary advice.
peer-reviewed systematic review with study-level RoB 2 assessment and no formal certainty grading
Population / model
4,656 participants across 15 unique randomized studies, mostly older adults in high- or upper-middle-income settings
Design / record
Evidence synthesis · exercise-only, multidomain, supplement and caloric-restriction programs with study-specific randomized comparators
Measured outcome
intrinsic capacity, quality of life and other multidimensional function or well-being scores
Publication state
Peer Reviewed
Governed result15 unique studies with 4,656 participants were synthesized qualitatively; 11 of 13 exercise or multidomain studies were labelled positive, with generally small effects and unclear clinical importance.
Evidence boundaryThe review maps heterogeneous multidimensional outcomes; it does not provide a pooled effect, treatment ranking, universal healthspan measure, individual recommendation or added healthy years.
peer-reviewed secondary composite analysis of a large randomized primary-prevention trial
Population / model
19,114 generally healthy community-dwelling older adults in Australia and the United States
Design / record
Randomized trial · 100 mg aspirin daily versus matching placebo
Measured outcome
time to first cardiovascular disease, diabetes, dementia, cancer or death event
Publication state
Peer Reviewed
Governed result82.1 versus 82.7 events per 1,000 person-years; HR 0.98, 95% CI 0.92–1.05.
Evidence boundaryThe estimate does not prove zero effect, isolate effects on the five components, measure years lived in good health or establish treatment advice.
peer-reviewed model-development and association evidence without external-biobank validation or demonstrated clinical utility
Population / model
MULTI Consortium model-development cohorts with linked UK Biobank, BLSA, ADNI and A4 analyses
Design / record
Observational study · female- and male-stratified reference models, with matched pooled models for selected internal comparisons; no clock-guided intervention
Measured outcome
chronological-age prediction, biological age gaps, genetic and molecular associations, incident disease, mortality and cognitive trajectories
Publication state
Peer Reviewed
Governed resultThe study built 38 sex-specific clocks across 15 organ systems; typical internal holdout MAE was about five years, with overfitting in several clocks and no external-biobank validation.
Evidence boundaryThe study did not validate a diagnosis, individual forecast, surrogate endpoint, treatment response, slower aging, healthspan or lifespan.
peer-reviewed Article in Press; single-center human prediction and association evidence without external validation
Population / model
7,837 adults in one University of Tokyo health-screening cohort; median age 54 and 63.8% male
Design / record
Observational study · CT-derived age gap compared with chronological age; no intervention or imaging-versus-no-imaging trial
Measured outcome
chronological-age prediction, prevalent disease, incident disease and discrimination statistics
Publication state
Peer Reviewed
Governed resultIn 7,837 adults, the model had R²=0.651 and MAE 4.63 years; each 1-SD higher age gap was associated with prevalent disease (OR 1.35) and incident disease (HR 1.24), with five-year tAUC 0.700 versus 0.688 for chronological age.
Evidence boundaryThe study did not establish causation, external validity, clinical utility, diagnosis, prevention benefit, slower aging or a reason to order CT imaging.
peer-reviewed exploratory human biomarker evidence from a selected disease-trial subset
Population / model
42 adults with idiopathic pulmonary fibrosis who consented to serum profiling and had complete four-timepoint samples; mean age 67.1
Design / record
Randomized trial · three rentosertib regimens versus placebo in a phase 2a IPF trial
Measured outcome
predicted-age change from six protein-based aging clocks
Publication state
Peer Reviewed
Governed resultTwenty-one of 54 regimen–time–clock comparisons met the authors’ Q<0.10 threshold, concentrated at week 4.
Evidence boundaryThe analysis did not establish clinical benefit, slower aging, healthspan, lifespan, healthy-person benefit or a validated surrogate endpoint.
Adult cigarette-smoking status, cessation timing, all-cause and cause-specific mortality, and modeled survival in the included national cohorts
Design / record
Evidence synthesis · cigarette smoking cessation; observational current and former cigarette smokers compared with never smokers; cessation timing compared with continued smoking
Measured outcome
Adult cigarette-smoking status, cessation timing, all-cause and cause-specific mortality, and modeled survival in the included national cohorts
Publication state
Peer Reviewed
Governed resultCho 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
Evidence boundaryA universal population estimate · An individual outcome · A product prescription · A claim of no conflicts · Proof of an exact causal effect
Adult cigarette-smoking status, cessation timing, all-cause and cause-specific mortality, and modeled survival in the included national cohorts
Design / record
Observational study · cigarette smoking cessation; observational current and former cigarette smokers compared with never smokers; cessation timing compared with continued smoking
Measured outcome
Adult cigarette-smoking status, cessation timing, all-cause and cause-specific mortality, and modeled survival in the included national cohorts
Publication state
Peer Reviewed
Governed resultJha 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
Evidence boundaryA randomized causal effect · An individualized forecast · Guaranteed years gained · A claim of no conflicts · Proof of an exact causal effect
Small three-arm randomized trial with self-reported fall-rate outcomes
Population / model
LiFE selected high-risk home-living population and measured fall outcomes
Design / record
Randomized trial · Lifestyle integrated Functional Exercise (LiFE); three-arm randomized parallel trial with fall calendars over 12 months; structured exercise and sham gentle exercise
Measured outcome
self-reported fall rate
Publication state
Peer Reviewed
Governed result317 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
Evidence boundaryInstitutionalized or general population · Fracture, disability, healthspan or lifespan · Cross-program ranking · Unsupervised instruction or injury guarantee
randomized human trial; indirect for longevity · research biomarker; clinical utility not established
Population / model
218 healthy, non-obese adults age 21–51
Design / record
Other human evidence · calorie restriction; randomized trial · epigenetic clocks; human validation evidence
Measured outcome
metabolism, cardiometabolic risk factors and DNA-methylation biomarkers
Publication state
Peer Reviewed
Governed resultA 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.
Evidence boundaryCALERIE tested calorie restriction for two years—not human lifespan · What an epigenetic clock can—and cannot—tell you
Large pragmatic cluster-randomized trial with a nonsignificant primary serious-injury result
Population / model
STRIDE selected primary-care population and measured fall outcomes
Design / record
Other human evidence · nurse-led multifactorial fall-injury prevention; pragmatic cluster-randomized trial across 86 primary-care practices; enhanced usual care with falls-prevention information
Measured outcome
time to first adjudicated serious fall injury
Publication state
Peer Reviewed
Governed result5,451 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
Evidence boundaryEvery multifactorial service · Significant primary reduction or equivalence · Replacement of the primary adjudicated result · Independence or lifespan benefit
Three-arm randomized trial with active comparators and separate follow-up evidence
Population / model
TJQMBB selected community population and measured fall outcomes
Design / record
Randomized trial · therapeutically tailored Tai Ji Quan (TJQMBB); single-blind three-arm randomized clinical trial; multimodal exercise and stretching
Measured outcome
incidence of falls during the six-month intervention
Publication state
Peer Reviewed
Governed result670 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
Evidence boundaryGeneric tai chi or other settings · Lifespan or guaranteed injury prevention · Universal superiority · Individual recommendation
Large randomized cardiovascular-outcome trial with an early-stopped intensive glycemia arm
Population / model
ACCORD cohort with independent ADVANCE countercontext
Design / record
Other human evidence · Different intensive and standard glucose-control strategies
Measured outcome
Safety and applicability
Publication state
Peer Reviewed
Governed resultAssistance-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.
Evidence boundaryNo single causal mechanism or cross-trial efficacy ranking
Large 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
Design / record
Randomized trial · 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
Measured outcome
HbA1c target and achieved levels; Nonfatal myocardial infarction, nonfatal stroke or cardiovascular death; All-cause mortality; Safety and applicability
Publication state
Peer Reviewed
Governed resultACCORD 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.
Evidence boundaryNo 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
Governed resultAt 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.
Evidence boundaryNo demonstrated cardiovascular, mortality, healthspan or lifespan benefit · No overall randomized microvascular benefit · No whole-cohort randomized microvascular effect
Human 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
Design / record
Randomized trial · Three annual low-dose CT screens versus chest radiography
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
Publication state
Peer Reviewed
Governed resultNLST 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.
Evidence boundaryDoes 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.
Human 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
Design / record
Observational study · Invitation to PSA-based screening about every four years versus control
Measured outcome
excess diagnosis and false positives
Publication state
Peer Reviewed
Governed resultRotterdam 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.
Evidence boundaryDoes not mean every additional diagnosis is harmful or that cancer-specific benefit erases urinary, sexual and other harms.
Human 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
Design / record
Randomized trial · Invitation to PSA-based screening about every four years versus control
Measured outcome
section-specific screening program · cancer-specific mortality and metastatic disease
Publication state
Peer Reviewed
Governed resultThe 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).
Evidence boundaryDoes 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.
Human 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
Design / record
Randomized trial · Invitation to PSA-based screening about every four years versus control
Measured outcome
section-specific screening program · cancer-specific mortality and metastatic disease
Publication state
Peer Reviewed
Governed resultThe 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).
Evidence boundaryDoes 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.
Human 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
Design / record
Randomized trial · Three annual low-dose CT screens versus chest radiography
Measured outcome
lung-cancer and all-cause mortality
Publication state
Peer Reviewed
Governed resultAt 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).
Evidence boundaryDoes not demonstrate a precise all-cause or longevity benefit.
Human cancer incidence and mortality · large randomized invitation trial
Population / model
84,583 men and women age 55–64 in Norway, Poland and Sweden
Design / record
Randomized trial · Invitation to one screening colonoscopy versus no screening invitation
Measured outcome
program offer and participation · short-term screening harms · all-cause mortality and current guidance
Publication state
Peer Reviewed
Governed resultNordICC 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.
Evidence boundaryDoes 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.
Human 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
Design / record
Randomized trial · Invitation to PSA-based screening about every four years versus control
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
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryDoes 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.
Human cancer incidence and mortality · large randomized invitation trial
Population / model
84,583 men and women age 55–64 in Norway, Poland and Sweden
Design / record
Randomized trial · Invitation to one screening colonoscopy versus no screening invitation
Measured outcome
program offer and participation · colorectal-cancer incidence · colorectal-cancer mortality · modeled outcomes under per-protocol assumptions
Publication state
Peer Reviewed
Governed resultNordICC 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.
Evidence boundaryDoes 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.
small 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
Design / record
Randomized trial · urolithin A; small randomized trial
Measured outcome
Four-month six-minute walk and ATP-production primary outcomes plus endurance and biomarker secondary outcomes
Publication state
Peer Reviewed
Governed resultENERGIZE 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
very 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
Design / record
Randomized trial · GlyNAC; very small randomized trial
Measured outcome
Two-week glutathione redox and oxidative-damage measures rather than longer-term function
Publication state
Peer Reviewed
Governed resultAn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
very 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
Design / record
Randomized trial · GlyNAC; very small randomized trial
Measured outcome
Sixteen-week registered glutathione outcome plus many metabolic, function and exploratory aging-hallmark measures
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Twelve-month mnemonic discrimination primary outcome plus prespecified secondary and exploratory outcomes
Publication state
Peer Reviewed
Governed resultSmartAge 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Plasma and salivary polyamines rather than cognitive or clinical outcomes
Publication state
Peer Reviewed
Governed resultA 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small 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
Design / record
Randomized trial · urolithin A; small randomized trial
Measured outcome
Primary peak-power outcome plus secondary strength, exercise and biomarker outcomes
Publication state
Peer Reviewed
Governed resultA related middle-aged-adult trial missed its peak-power primary endpoint, and neither trial validates other urolithin A, pomegranate, microbiome or retail formulations.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Randomized trial · low-dose aspirin; large randomized trial
Measured outcome
Cardiovascular composite and major hemorrhage over median 4.7 years
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized-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
Design / record
Randomized trial · low-dose aspirin; randomized trial plus observational extension
Measured outcome
All-cause and cause-specific mortality over median 4.7 years
Publication state
Peer Reviewed
Governed resultAll-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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Randomized trial · low-dose aspirin; large randomized trial
Measured outcome
Disability-free survival composite and components over median 4.7 years
Publication state
Peer Reviewed
Governed resultASPREE 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized-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
Design / record
Randomized trial · low-dose aspirin; randomized trial plus observational extension
Measured outcome
Cancer incidence and mortality across combined and post-trial follow-up
Publication state
Peer Reviewed
Governed resultASPREE-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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small 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
Design / record
Other human evidence · habitual winter swimming and cold challenge; cross-sectional swimmer versus matched comparison group
Measured outcome
Brown-fat activity, thermogenesis and laboratory physiology measures
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Other human evidence · testosterone; large randomized noninferiority trial
Measured outcome
Requested limitation-of-use, prostate-cancer, and benign-prostatic-hyperplasia label revisions
Publication state
Publication Record
Governed resultOn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Other human evidence · low-dose aspirin; large randomized trial · low-dose aspirin; large randomized trial · low-dose aspirin; randomized trial plus observational extension
Measured outcome
Bleeding, interaction and clinician-guidance context
Publication state
Publication Record
Governed resultASPREE 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.
Evidence boundaryASPREE 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
large 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
Design / record
Other human evidence · testosterone; large randomized noninferiority trial
Measured outcome
Cardiovascular boxed-warning language and class-wide blood-pressure warnings
Publication state
Publication Record
Governed resultOn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small 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
Design / record
Other human evidence · supervised hyperbaric-oxygen research program; single-arm pre/post study without a control
Measured outcome
Telomere length and senescent-cell proportions in selected peripheral blood mononuclear cell subtypes
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
long 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
Design / record
Evidence synthesis · habitual sauna use; prospective cohort by self-reported frequency
Measured outcome
Short-term surrogate cardiometabolic and vascular outcomes, not mortality
Publication state
Peer Reviewed
Governed resultA 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
long 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
Design / record
Observational study · habitual sauna use; prospective cohort by self-reported frequency
Measured outcome
Sudden cardiac death, fatal coronary heart disease, fatal cardiovascular disease and all-cause mortality over median 20.7 years
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Randomized trial · testosterone; large randomized noninferiority trial
Measured outcome
Time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke
Publication state
Peer Reviewed
Governed resultTRAVERSE 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Time to first clinical fracture over median 3.19 years
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
One-year volumetric bone mineral density and estimated bone strength
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Sexual function, six-minute walk physical function, vitality, mood, and short-term safety over one year
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
human 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
Design / record
Other human evidence · testosterone; one-year randomized trials
Measured outcome
Six-minute walk distance, self-reported walking ability, and falls
Publication state
Peer Reviewed
Governed resultAcross 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Other human evidence · low-dose aspirin; large randomized trial · low-dose aspirin; large randomized trial
Measured outcome
Dated initiation recommendation by age
Publication state
Publication Record
Governed resultThe April 26, 2022 USPSTF recommendation advises against initiating low-dose aspirin for primary CVD prevention in adults 60 or older.
Evidence boundaryASPREE found no gain in disability-free survival—and more major bleeding · ASPREE did not lower cardiovascular events—and increased major bleeding
randomized 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
Design / record
Other human evidence · cognitive training; randomized trial plus disputed secondary analysis
Measured outcome
claims-diagnosed ADRD in randomized arms and post-randomization booster subgroups
Publication state
Peer Reviewed
Governed resultA 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized 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
Design / record
Other human evidence · cognitive training; randomized trial plus disputed secondary analysis
Measured outcome
comparability, selection, claims diagnosis, prespecification and multiplicity limitations
Publication state
Peer Reviewed
Governed resultThe ACTIVE booster subgroup result is contested over comparability, selection, claims diagnosis, lack of prespecification and multiplicity; the authors published a response.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized 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
Design / record
Other human evidence · cognitive training; randomized trial plus disputed secondary analysis
Measured outcome
response to published methodological criticism
Publication state
Peer Reviewed
Governed resultThe ACTIVE booster subgroup result is contested over comparability, selection, claims diagnosis, lack of prespecification and multiplicity; the authors published a response.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
trained memory, reasoning and speed-of-processing abilities
Publication state
Peer Reviewed
Governed resultACTIVE 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
trained-domain persistence and instrumental daily-activity outcomes
Publication state
Peer Reviewed
Governed resultACTIVE 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
three 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
Design / record
Randomized trial · RSV vaccines; three randomized vaccine trials
Measured outcome
RT-PCR-confirmed RSV lower-respiratory-tract disease, acute respiratory infection and safety over the first season
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
polysomnographic and diary sleep outcomes over six weeks and follow-up
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Other human evidence · influenza vaccine; large randomized trial
Measured outcome
preferential product categories and the fallback when a preferred product is unavailable
Publication state
Publication Record
Governed resultFor 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
three 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
Design / record
Other human evidence · RSV vaccines; three randomized vaccine trials
Measured outcome
current one-dose recommendation, product-neutral guidance, timing and repeat-dose uncertainty
Publication state
Publication Record
Governed resultCDC 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
three 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
Design / record
Randomized trial · RSV vaccines; three randomized vaccine trials
Measured outcome
RSV lower-respiratory-tract disease by two- and three-symptom definitions, acute respiratory disease and safety
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
three 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
Design / record
Observational study · RSV vaccines; three randomized vaccine trials
Measured outcome
postmarketing Guillain–Barré syndrome signal and labeling warning
Publication state
Publication Record
Governed resultFDA 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
strong randomized shingles-prevention evidence with emerging observational and quasi-experimental dementia evidence
Population / model
people within current U.S. Shingrix labeled indications
Design / record
Other human evidence · shingles vaccine; randomized and non-randomized evidence
Measured outcome
approved prevention indication and labeled population, excluding dementia prevention
Publication state
Publication Record
Governed resultCurrent evidence does not establish recombinant zoster vaccination as a causal dementia-prevention treatment or an FDA-approved dementia indication.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Randomized trial · influenza vaccine; large randomized trial
Measured outcome
protocol-defined laboratory-confirmed influenza with illness, immunogenicity and safety
Publication state
Peer Reviewed
Governed resultAcross 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large randomized human fracture evidence plus outcome-specific duration and current regulator safety context
Population / model
women completing three years of HORIZON zoledronic-acid treatment
Design / record
Randomized trial · zoledronic acid; large randomized trial
Measured outcome
fractures, BMD and safety after continuing to six years or stopping at three
Publication state
Peer Reviewed
Governed resultContinuing 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Randomized trial · zoledronic acid; large randomized trial
Measured outcome
morphometric vertebral, hip and other fracture outcomes over three years
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Randomized trial · CPAP; large randomized trials
Measured outcome
cardiovascular events over median 3.35 years
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
sleep outcomes and remission after behavioral treatment
Publication state
Peer Reviewed
Governed resultA 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small 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
Design / record
Other human evidence · LIFTMOR; small supervised randomized trial
Measured outcome
table-heading and calcium-intake-change corrections
Publication state
Peer Reviewed
Governed resultThe LIFTMOR erratum corrected table headings and the sign of calcium-intake change; it did not create or reverse a bone or fracture outcome.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small 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
Design / record
Randomized trial · LIFTMOR; small supervised randomized trial
Measured outcome
eight-month BMD, strength, function, adherence and reported adverse events
Publication state
Peer Reviewed
Governed resultLIFTMOR 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small 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
Design / record
Randomized trial · LIFTMOR; small supervised randomized trial
Measured outcome
vertebral morphology and incident vertebral fracture during the supervised program
Publication state
Peer Reviewed
Governed resultOne 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
strong 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
Design / record
Observational study · shingles vaccine; randomized and non-randomized evidence
Measured outcome
new recorded dementia diagnosis over seven years after eligibility for live-attenuated zoster vaccine
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized 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
Design / record
Randomized trial · MIND diet; randomized dietary trial
Measured outcome
three-year global cognition and MRI measures
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
sleep latency, sleep quality, morning alertness and safety
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
strong 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
Design / record
Observational study · shingles vaccine; randomized and non-randomized evidence
Measured outcome
recorded dementia diagnoses during up to six years after live or recombinant zoster vaccination
Publication state
Peer Reviewed
Governed resultA 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
three 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
Design / record
Randomized trial · RSV vaccines; three randomized vaccine trials
Measured outcome
RSV lower-respiratory-tract illness by two- and three-symptom definitions, acute respiratory illness and safety
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large 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
Design / record
Randomized trial · CPAP; large randomized trials
Measured outcome
composite serious cardiovascular events plus symptoms and quality of life
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
sleep quality and morning alertness after prolonged-release melatonin
Publication state
Peer Reviewed
Governed resultA 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
chronic-disease, cancer, thromboembolism and fracture outcomes over mean 5.2 years
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
clinical-practice interpretation of WHI randomized evidence
Publication state
Peer Reviewed
Governed resultWHI 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
all-cause and cause-specific mortality through 18 years
Publication state
Peer Reviewed
Governed resultAcross 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
strong randomized shingles-prevention evidence with emerging observational and quasi-experimental dementia evidence
Population / model
15,411 evaluable adults age 50 or older
Design / record
Randomized trial · shingles vaccine; randomized and non-randomized evidence
Measured outcome
laboratory and clinically confirmed herpes zoster over mean 3.2 years plus solicited and serious adverse events
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized human evidence with secondary subgroup analysis
Population / model
977 adults aged 70–84
Design / record
Randomized trial · hearing; randomized trial with subgroup signals
Measured outcome
three-year global cognition
Publication state
Peer Reviewed
Governed resultAcross 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized human trials, subgroup analyses, extended follow-up, and individual-participant meta-analysis
Population / model
Adults aged 65 and older without baseline atherosclerotic cardiovascular disease
Design / record
Randomized trial · statins; trials and pooled evidence
Measured outcome
all-cause mortality and coronary events
Publication state
Peer Reviewed
Governed resultPROSPER'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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
global cognition, episodic memory, executive function, and attention
Publication state
Peer Reviewed
Governed resultCOSMOS 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Governed resultA 2026 COSMOS analysis found modest movement in two DNA-methylation clocks, but did not establish better clinical aging, lower mortality, or longer life.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
telephone cognitive-test composites over three years
Publication state
Peer Reviewed
Governed resultCOSMOS 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
immediate recall, retention, executive function, and object recognition
Publication state
Peer Reviewed
Governed resultCOSMOS 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Randomized trial · creatine; trials and pooled evidence
Measured outcome
one-year bone area and muscle density
Publication state
Peer Reviewed
Governed resultOne-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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Randomized trial · creatine; trials and pooled evidence
Measured outcome
one-year bone, muscle, strength and adverse events
Publication state
Peer Reviewed
Governed resultOne-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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Evidence synthesis · creatine; trials and pooled evidence
Measured outcome
DXA lean tissue and chest/leg press strength
Publication state
Peer Reviewed
Governed resultCreatine 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized human trials, subgroup analyses, extended follow-up, and individual-participant meta-analysis
Population / model
Participants in 28 randomized statin trials across age groups
Design / record
Evidence synthesis · statins; trials and pooled evidence
Measured outcome
major vascular events and mortality
Publication state
Peer Reviewed
Governed resultPROSPER'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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Randomized trial · meal timing; short randomized trials
Measured outcome
14-week weight, fat and cardiometabolic outcomes
Publication state
Peer Reviewed
Governed resultOther 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small randomized human trials dominated by cognitive tests and metabolic or cardiovascular surrogate endpoints
Population / model
74 men with metabolic syndrome
Design / record
Randomized trial · resveratrol; small heterogeneous trials
Measured outcome
metabolic outcomes and laboratory safety signals
Publication state
Peer Reviewed
Governed resultSeveral 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small randomized human trials dominated by cognitive tests and metabolic or cardiovascular surrogate endpoints
Population / model
45 overweight or slightly obese adults
Design / record
Randomized trial · resveratrol; small heterogeneous trials
Measured outcome
lipid, glucose, inflammation, and endothelial markers
Publication state
Peer Reviewed
Governed resultSeveral controlled resveratrol trials found no meaningful improvement in metabolic or cardiovascular surrogate outcomes in their tested populations.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
composite cardiovascular events, atrial fibrillation, and bleeding
Publication state
Peer Reviewed
Governed resultVITAL 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small randomized human trials dominated by cognitive tests and metabolic or cardiovascular surrogate endpoints
Population / model
24 obese men
Design / record
Randomized trial · resveratrol; small heterogeneous trials
Measured outcome
insulin sensitivity, substrate metabolism, and body composition
Publication state
Peer Reviewed
Governed resultSeveral 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized human trials, subgroup analyses, extended follow-up, and individual-participant meta-analysis
Population / model
PROSPER cognitive substudy participants
Design / record
Randomized trial · statins; trials and pooled evidence
Measured outcome
cognitive performance
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized human trials, subgroup analyses, extended follow-up, and individual-participant meta-analysis
Population / model
PROSPER participants linked to long-term outcomes
Design / record
Randomized trial · statins; trials and pooled evidence
Measured outcome
mortality, vascular outcomes, and cancer
Publication state
Peer Reviewed
Governed resultThe 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized 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
Design / record
Randomized trial · statins; trials and pooled evidence
Measured outcome
coronary death, nonfatal myocardial infarction, and stroke
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Governed resultPrescription 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large randomized human cardiovascular-outcomes evidence with secondary and post-trial cognitive follow-up
Population / model
surviving SPRINT participants after the randomized treatment period
Design / record
Randomized trial · blood pressure; large randomized trial
Measured outcome
later cognitive outcomes
Publication state
Peer Reviewed
Governed resultSPRINT MIND did not significantly reduce probable dementia; its favorable mild-cognitive-impairment result was secondary and SPRINT did not test biological aging or lifespan.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large randomized human cardiovascular-outcomes evidence with secondary and post-trial cognitive follow-up
Population / model
SPRINT participants with adjudicated cognitive follow-up
Design / record
Randomized trial · blood pressure; large randomized trial
Measured outcome
probable dementia and mild cognitive impairment
Publication state
Peer Reviewed
Governed resultSPRINT MIND did not significantly reduce probable dementia; its favorable mild-cognitive-impairment result was secondary and SPRINT did not test biological aging or lifespan.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Randomized trial · meal timing; short randomized trials
Measured outcome
12-week MRI visceral fat and safety
Publication state
Peer Reviewed
Governed resultOther 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Randomized trial · meal timing; short randomized trials
Measured outcome
12-week weight and metabolic outcomes
Publication state
Peer Reviewed
Governed resultTREAT 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Governed resultVITAL 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large randomized human cancer, cardiovascular, and fracture outcome evidence
Population / model
VITAL participants not selected for deficiency, low bone mass, or osteoporosis
Design / record
Randomized trial · vitamin D; large randomized prevention trial
Measured outcome
total, nonvertebral, and hip fractures
Publication state
Peer Reviewed
Governed resultVitamin 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
large randomized human cancer, cardiovascular, and fracture outcome evidence
Population / model
25,871 generally healthy US adults
Design / record
Randomized trial · vitamin D; large randomized prevention trial
Measured outcome
invasive cancer and major cardiovascular events
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small randomized human trials dominated by cognitive tests and metabolic or cardiovascular surrogate endpoints
Population / model
healthy overweight older adults
Design / record
Randomized trial · resveratrol; small heterogeneous trials
Measured outcome
memory-test performance, glucose metabolism, and hippocampal connectivity
Publication state
Peer Reviewed
Governed resultOne 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Other human evidence · exercise; mature randomized evidence
Measured outcome
mobility, function, frailty, falls and all-cause mortality
Publication state
Peer Reviewed
Governed resultHuman trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
all-cause mortality; cardiovascular mortality; cancer mortality
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Other human evidence · exercise; mature randomized evidence
Measured outcome
mobility, function, frailty, falls and all-cause mortality
Publication state
Peer Reviewed
Governed resultHuman trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized human evidence for specific functional outcomes; lifespan evidence unavailable
Population / model
370 hospitalized adults, mean age 87.3
Design / record
Randomized trial · exercise; randomized trials
Measured outcome
discharge function
Publication state
Peer Reviewed
Governed resultA brief supervised inpatient program improved discharge function in one very-old population. · The featured physical-activity trials do not establish lifespan extension.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized human evidence for specific functional outcomes; lifespan evidence unavailable
Population / model
1,635 adults aged 70–89
Design / record
Randomized trial · exercise; randomized trials
Measured outcome
major mobility disability
Publication state
Peer Reviewed
Governed resultThe LIFE program reduced major mobility disability in its enrolled older population. · The featured physical-activity trials do not establish lifespan extension.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Other human evidence · partial reprogramming; no results yet
Measured outcome
planned safety, dose-limiting toxicity, laboratory and eye measures; no posted results
Publication state
Peer Reviewed
Governed resultA 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
small 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
Design / record
Randomized trial · metformin; small trials
Measured outcome
lean mass; thigh muscle mass; muscle area and density; strength
Publication state
Peer Reviewed
Governed resultDuring 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Observational study · sleep; mostly observational evidence
Measured outcome
all-cause mortality association
Publication state
Peer Reviewed
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
early randomized human biomarker and short-term physiological evidence; no lifespan evidence
Population / model
13 overweight or obese adults
Design / record
Randomized trial · NAD biology; small trials
Measured outcome
metabolic physiology and NAD metabolites
Publication state
Peer Reviewed
Governed resultOral 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
early randomized human biomarker and short-term physiological evidence; no lifespan evidence
Population / model
24 completers
Design / record
Randomized trial · NAD biology; small trials
Measured outcome
NAD metabolites and exploratory physiology
Publication state
Peer Reviewed
Governed resultOral 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Other human evidence · partial reprogramming; no results yet
Measured outcome
planned safety, dose-limiting toxicity, laboratory and eye measures; no posted results
Publication state
Peer Reviewed
Governed resultA 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Governed resultIn 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.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
randomized disease-outcome evidence and approved population-specific cardiovascular indication
Population / model
17,604 adults with CVD and BMI at least 27, without diabetes
Design / record
Randomized trial · GLP-1 drugs; large randomized trial
Measured outcome
major cardiovascular events
Publication state
Peer Reviewed
Governed resultSemaglutide reduced SELECT's major cardiovascular event composite in its enrolled population. · SELECT did not test aging reversal, healthspan, or lifespan extension.
Evidence boundaryThe measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
MIRAILAB BIOSCIENCE is the monetary-support/secondary sponsor; company roles and author employment are reported in the linked analysis.
Population / model
62 selected healthy Japanese adults age 65 or older randomized at one center
Design / record
Registered clinical trial · 1,250 mg/day oral NMN versus matched placebo for 24 weeks
Measured outcome
Change from baseline in hearing ability after 24 weeks; manuscript specifies a four-frequency pure-tone average
Operational status
Complete · Phase not-applicable
Results availability
Peer-reviewed publication linked
Governed resultWhole-blood NAD rose markedly, while the registered hearing outcome and measured physical function did not show attributable improvement.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
University of Nottingham sponsor; NIHR Nottingham Biomedical Research Centre award NIHR203310; declared author relationships are reported in the linked analysis.
Population / model
31 adults older than 65 with frailty or pre-frailty randomized at one Nottingham centre; 29 completed; most were pre-frail
Design / record
Registered clinical trial · 10 g/day low-methoxy citrus pectin plus whey/cocoa versus matched whey/cocoa without pectin for four weeks
Measured outcome
Registry version 1 listed microbiome profile, inflammatory profile and serum short-chain fatty acids as primary outcomes; the paper reports a different hierarchy and did not measure SCFAs.
Operational status
Recruiting (registry not updated to paper-reported completion) · Phase not-applicable
Results availability
No registry results posted
Governed resultThe paper-defined TNF-α, IFN-γ and zonulin outcomes showed no significant between-group change; secondary physical, psychological and exploratory microbiome signals require replication. · Outcome labels are a map of the trial's questions, not a truth score; multiplicity, interaction tests, analysis populations, effect size, uncertainty and replication remain separate checks.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
BrightFocus Foundation funding; Dr Timothy Sargeant listed as primary sponsor. Two authors are inventors on a related autophagic-flux-assay patent.
Population / model
healthy adults age 20–50 with BMI 18.5–29.9; 74 randomized, 63 completed both diet periods
Design / record
Registered clinical trial · 10% versus 20% of energy from protein for 4 weeks each, separated by a 4-week washout, at calculated energy balance
Measured outcome
fasting whole-blood/PBMC autophagic flux measured by LC3B-II turnover during lysosomal inhibition
Operational status
Completed · Phase not-applicable
Results availability
Peer-reviewed publication linked
Governed resultA 4-week diet providing 10% rather than 20% of energy from protein did not produce a detectable average increase in fasting PBMC autophagic flux.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
19,114 community-dwelling older adults without cardiovascular disease at enrollment
disability-free survival (death, dementia or persistent physical disability)
Operational status
Unknown
Results availability
No registry results posted
Governed resultA secondary analysis found 82.1 versus 82.7 events per 1,000 person-years; HR 0.98, 95% CI 0.92–1.05. · In selected older adults without cardiovascular disease, low-dose aspirin did not significantly reduce the trial’s cardiovascular composite. Major hemorrhage occurred more often. · 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. · 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
A4 used a public-private-philanthropic partnership including NIH/NIA and Eli Lilly; the clock paper reports the linked support and no competing interests.
Population / model
1,169 randomized cognitively unimpaired adults age 65 to 85 with elevated brain amyloid; 1,055 had baseline MRI in the 2026 secondary analysis
Design / record
Registered clinical trial · monthly intravenous solanezumab versus placebo over 240 weeks in A4; secondary 2026 analyses grouped participants by brain-age gap
Measured outcome
Preclinical Alzheimer Cognitive Composite change; the primary A4 result did not show slowed cognitive decline with solanezumab
Operational status
Completed · Phase phase-3
Results availability
Peer-reviewed publication linked
Governed resultThe secondary analysis reported cognitive-trajectory associations through week 240.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
The trial and ancillary analysis involved InSilico Medicine, which developed rentosertib; the ancillary paper reports no specific funding and discloses company affiliations.
Population / model
71 adults older than 40 with idiopathic pulmonary fibrosis at 21 sites in China; 42 contributed complete serum samples to the ancillary proteomic analysis
Design / record
Registered clinical trial · three oral rentosertib regimens versus placebo over 12 weeks
Measured outcome
treatment-emergent adverse events; FVC outcomes were secondary, and proteomic-clock outcomes were ancillary
Operational status
Completed · Phase phase-2
Results availability
Peer-reviewed publication linked
Governed resultTwenty-one of 54 regimen–time–clock comparisons met the authors’ Q<0.10 threshold, concentrated at week 4.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
9,361 adults age 50 or older at elevated cardiovascular risk, without diabetes or prior stroke
Design / record
Registered clinical trial · large randomized trial
Measured outcome
cardiovascular events, mortality, adverse events and cognitive outcomes
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultIntensive treatment lowered cardiovascular events and mortality in eligible high-risk adults, with more hypotension, electrolyte problems and kidney injury.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
sleep latency, sleep efficiency, insomnia remission and durability
Operational status
Unknown
Results availability
Peer-reviewed publication linked
Governed resultTwo randomized trials support meaningful sleep improvement in older adults; they did not test dementia prevention, biological aging or lifespan.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
sleep latency, sleep efficiency, insomnia remission and durability
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultTwo randomized trials support meaningful sleep improvement in older adults; they did not test dementia prevention, biological aging or lifespan.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
NIH-supported trial and follow-ups; the 20-year mortality report declared no conflicts, while commercial descendants are not evidence for the studied protocol.
Population / model
2,832 independent U.S. adults age 65–94
Design / record
Registered clinical trial · randomized trial plus disputed secondary analysis
Measured outcome
trained abilities, daily function, all-cause mortality and claims-diagnosed dementia
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultACTIVE supports trained-ability gains and some function signals, found no mortality benefit, and leaves a claims-based dementia subgroup methodologically disputed. · Outcome labels are a map of the trial's questions, not a truth score; multiplicity, interaction tests, analysis populations, effect size, uncertainty and replication remain separate checks.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
SAVE reported support from public agencies and Philips Respironics; ISAACC reported public and industry support. Treatment adherence and selected populations limit inference.
Population / model
2,717 adults with sleep apnea and cardiovascular or cerebrovascular disease; 1,264 non-sleepy adults after acute coronary syndrome
Design / record
Registered clinical trial · large randomized trials
Measured outcome
major cardiovascular events, sleepiness, symptoms and quality of life
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultSAVE and ISAACC did not significantly reduce their primary cardiovascular outcomes; SAVE separately found symptom and quality-of-life benefits.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
SAVE reported support from public agencies and Philips Respironics; ISAACC reported public and industry support. Treatment adherence and selected populations limit inference.
Population / model
2,717 adults with sleep apnea and cardiovascular or cerebrovascular disease; 1,264 non-sleepy adults after acute coronary syndrome
Design / record
Registered clinical trial · large randomized trials
Measured outcome
major cardiovascular events, sleepiness, symptoms and quality of life
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultSAVE and ISAACC did not significantly reduce their primary cardiovascular outcomes; SAVE separately found symptom and quality-of-life benefits.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
mobility, function, frailty, falls and all-cause mortality
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultHuman trials support mobility and physical function in defined populations. Lifespan and biological-age claims require separate evidence. · LIFE supports a meaningful mobility outcome in vulnerable older adults, while lifespan and universal-program claims remain untested.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Public and nonprofit research funding; the primary report lists investigator disclosures and does not establish an intervention-component sponsor effect.
Population / model
1,260 Finnish adults age 60–77 at elevated dementia risk and with average-to-lower cognitive performance
Governed resultA 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
Very small sample of older adults
Design / record
Registered clinical trial · very small randomized trial
Measured outcome
biomarkers and physical function
Operational status
Completed
Results availability
No registry results posted
Governed resultA 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
Very small selected sample of young healthy men
Design / record
Registered clinical trial · cross-sectional swimmer versus matched comparison group
Measured outcome
brown-fat activity and thermogenesis
Operational status
Completed
Results availability
Not assessed
Governed resultA 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
Very small selected sample of young healthy men
Design / record
Registered clinical trial · cross-sectional swimmer versus matched comparison group
Measured outcome
brown-fat activity and thermogenesis
Operational status
Completed
Results availability
Not assessed
Governed resultA 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
977 community-dwelling adults age 70–84 with untreated hearing loss
Design / record
Registered clinical trial · randomized trial with subgroup signals
Measured outcome
three-year standardized global-cognition change
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultThe three-year trial was null across its full cohort. Signals in higher-risk groups need confirmation and do not establish dementia prevention.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
5,145 adults age 45–75 with type 2 diabetes and overweight or obesity
Design / record
Registered clinical trial · intensive lifestyle intervention versus diabetes support and education
Measured outcome
major cardiovascular events, weight and cardiometabolic risk factors
Operational status
Completed
Results availability
Not assessed
Governed resultThe 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
2,776 surviving DPP participants with elevated glucose and overweight or obesity who joined long-term follow-up
Design / record
Registered clinical trial · randomized lifestyle or metformin versus placebo, followed observationally after the original trial
Measured outcome
cumulative type 2 diabetes incidence and aggregate microvascular disease
Operational status
Completed
Results availability
Not assessed
Governed resultOver 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
2,776 surviving DPP participants with elevated glucose and overweight or obesity who joined long-term follow-up
Design / record
Registered clinical trial · randomized lifestyle or metformin versus placebo, followed observationally after the original trial
Measured outcome
cumulative type 2 diabetes incidence and aggregate microvascular disease
Operational status
Active, not recruiting · Phase phase-3
Results availability
Not assessed
Governed resultOver 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
10,251 adults with established type 2 diabetes and high cardiovascular risk
Design / record
Registered clinical trial · intensive glycemia target below 6% versus standard target of 7.0% to 7.9%
Measured outcome
major cardiovascular events, all-cause mortality and treatment harms
Operational status
Completed
Results availability
Not assessed
Governed resultThe 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
Adults with overweight or obesity in three trials lasting 12–14 weeks
Design / record
Registered clinical trial · short randomized trials
Measured outcome
weight, body composition, visceral fat and cardiometabolic markers
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultDifferent eating windows and comparators produced different weight and fat findings; none tested biological aging, healthspan or lifespan.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
Adults with overweight or obesity in three trials lasting 12–14 weeks
Design / record
Registered clinical trial · short randomized trials
Measured outcome
weight, body composition, visceral fat and cardiometabolic markers
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultDifferent eating windows and comparators produced different weight and fat findings; none tested biological aging, healthspan or lifespan.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
Adults with overweight or obesity in three trials lasting 12–14 weeks
Design / record
Registered clinical trial · short randomized trials
Measured outcome
weight, body composition, visceral fat and cardiometabolic markers
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultDifferent eating windows and comparators produced different weight and fat findings; none tested biological aging, healthspan or lifespan.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
myocardial infarction, stroke or cardiovascular death
Operational status
Unknown
Results availability
Not assessed
Governed resultThe corrected randomized analysis is promising for its composite endpoint, while allocation deviations and lifespan limits remain visible.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
The featured prolonged-release melatonin trial was funded by Neurim; several authors disclosed employee, consultant, owner or leadership roles. Product formulation and jurisdiction matter.
Population / model
791 adults in one age-effects trial; 354 adults age 55–80 in a separate insomnia trial
sleep latency, sleep quality and morning alertness
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultSpecific prolonged-release melatonin trials reported modest sleep benefits; they did not test biological-age reversal, healthspan or lifespan.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
NIH/NHLBI sponsored the WHI hormone trials; Wyeth-Ayerst donated study drugs. Regimen-specific disclosures remain visible.
Population / model
Postmenopausal women age 50–79, separated by uterus status and hormone regimen
Design / record
Registered clinical trial · randomized trials
Measured outcome
disease events, breast cancer and all-cause mortality
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultWHI found a formulation-specific mix of benefits and harms, no overall 18-year mortality difference, and no basis for general longevity prevention.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Governed resultBoth groups improved with counseling and calorie restriction; the between-group cognitive difference was not significant and MRI measures were similar.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
cognitive-test scores, word recall and DNA-methylation biomarkers
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultCOSMOS found small cognitive-test differences and modest movement in two DNA-methylation clocks; neither establishes dementia prevention or longer life.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
cognitive-test scores, word recall and DNA-methylation biomarkers
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultCOSMOS found small cognitive-test differences and modest movement in two DNA-methylation clocks; neither establishes dementia prevention or longer life.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
Mostly middle-aged or older adults with differing health profiles
Design / record
Registered clinical trial · small trials
Measured outcome
metabolites, physiology and short-term function
Operational status
Unknown
Results availability
Peer-reviewed publication linked
Governed resultSmall trials show target engagement, not broad clinical, healthspan or lifespan benefit—and products and routes are not interchangeable.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
Mostly middle-aged or older adults with differing health profiles
Design / record
Registered clinical trial · small trials
Measured outcome
metabolites, physiology and short-term function
Operational status
Unknown
Results availability
Peer-reviewed publication linked
Governed resultSmall trials show target engagement, not broad clinical, healthspan or lifespan benefit—and products and routes are not interchangeable.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
Mostly middle-aged or older adults with differing health profiles
Design / record
Registered clinical trial · small trials
Measured outcome
metabolites, physiology and short-term function
Operational status
Completed
Results availability
Not assessed
Governed resultSmall trials show target engagement, not broad clinical, healthspan or lifespan benefit—and products and routes are not interchangeable.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
cardiovascular composites and components, mortality, atrial fibrillation and bleeding
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultTwo mixed EPA+DHA trials were neutral on primary outcomes; prescription icosapent ethyl benefited a defined high-risk population with safety and comparator limits. · In generally healthy adults, vitamin D3 did not significantly reduce invasive cancer, major cardiovascular events, or fractures; deficiency treatment is a different question.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
cardiovascular composites and components, mortality, atrial fibrillation and bleeding
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultTwo mixed EPA+DHA trials were neutral on primary outcomes; prescription icosapent ethyl benefited a defined high-risk population with safety and comparator limits.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
cardiovascular composites and components, mortality, atrial fibrillation and bleeding
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultTwo mixed EPA+DHA trials were neutral on primary outcomes; prescription icosapent ethyl benefited a defined high-risk population with safety and comparator limits.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Population / model
18 adults age 40–85 with glaucoma or recent non-arteritic anterior ischemic optic neuropathy (planned enrollment)
Design / record
Registered clinical trial · no results yet
Measured outcome
planned safety, dose-limiting toxicity, laboratory and eye measures; no posted results
Operational status
Recruiting · Phase phase-1
Results availability
No registry results posted
Governed resultA 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Mixed investigator, public, and public-private support; some study products were manufacturer supplied.
Population / model
Healthy overweight older adults, obese men, older exercising men and men with metabolic syndrome
Design / record
Registered clinical trial · small heterogeneous trials
Measured outcome
memory tests, metabolic markers, body composition, inflammation and exercise adaptation
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultOne small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Mixed investigator, public, and public-private support; some study products were manufacturer supplied.
Population / model
Healthy overweight older adults, obese men, older exercising men and men with metabolic syndrome
Design / record
Registered clinical trial · small heterogeneous trials
Measured outcome
memory tests, metabolic markers, body composition, inflammation and exercise adaptation
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultOne small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Mixed investigator, public, and public-private support; some study products were manufacturer supplied.
Population / model
Healthy overweight older adults, obese men, older exercising men and men with metabolic syndrome
Design / record
Registered clinical trial · small heterogeneous trials
Measured outcome
memory tests, metabolic markers, body composition, inflammation and exercise adaptation
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultOne small memory-test signal sits beside several null or unfavorable metabolic trials; human evidence does not show longer life or healthspan.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
Adults age 60 or older across three separate pivotal vaccine trials
Design / record
Registered clinical trial · three randomized vaccine trials
Measured outcome
RSV lower-respiratory disease or illness, acute respiratory disease and safety
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultArexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
Adults age 60 or older across three separate pivotal vaccine trials
Design / record
Registered clinical trial · three randomized vaccine trials
Measured outcome
RSV lower-respiratory disease or illness, acute respiratory disease and safety
Operational status
Active, not recruiting · Phase phase-3
Results availability
Peer-reviewed publication linked
Governed resultArexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
Adults age 60 or older across three separate pivotal vaccine trials
Design / record
Registered clinical trial · three randomized vaccine trials
Measured outcome
RSV lower-respiratory disease or illness, acute respiratory disease and safety
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultArexvy, Abrysvo and mResvia each reduced a trial-defined RSV respiratory endpoint, but separate protocols cannot establish a product ranking.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
Adults age 50 or older in ZOE-50 plus older vaccine-eligible cohorts in two dementia analyses
Design / record
Registered clinical trial · randomized and non-randomized evidence
Measured outcome
herpes-zoster disease and recorded dementia diagnoses
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultRandomized trials established shingles prevention. Dementia findings come from observational and quasi-experimental studies and do not prove prevention.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
5,204 TRAVERSE participants: middle-aged and older men with symptoms, repeatedly low testosterone and preexisting or high cardiovascular risk
Design / record
Registered clinical trial · randomized trials
Measured outcome
clinical fractures and bone-density measures
Operational status
Completed
Results availability
Registry results posted
Governed resultClinical fractures were more frequent with testosterone than placebo in TRAVERSE; a smaller substudy’s bone-density gain cannot substitute for fracture outcomes. · 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
5,204 TRAVERSE participants: middle-aged and older men with symptoms, repeatedly low testosterone and preexisting or high cardiovascular risk
Design / record
Registered clinical trial · randomized trials
Measured outcome
clinical fractures and bone-density measures
Operational status
Completed
Results availability
Registry results posted
Governed resultClinical fractures were more frequent with testosterone than placebo in TRAVERSE; a smaller substudy’s bone-density gain cannot substitute for fracture outcomes. · 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
Selected older adults with lower mitochondrial function
Design / record
Registered clinical trial · small randomized trial
Measured outcome
walking distance, muscle endurance and ATP production
Operational status
Completed
Results availability
No registry results posted
Governed resultENERGIZE 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Primarily NIH-funded; vitamin D was donated by Pharmavite.
Population / model
25,871 generally healthy U.S. adults not selected for vitamin D deficiency, low bone mass or osteoporosis
Design / record
Registered clinical trial · large randomized prevention trial
Measured outcome
invasive cancer, major cardiovascular events and clinical fractures
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultIn generally healthy adults, vitamin D3 did not significantly reduce invasive cancer, major cardiovascular events, or fractures; deficiency treatment is a different question.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
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.
Population / model
Older adults with subjective cognitive decline
Design / record
Registered clinical trial · small randomized phase 2b trial
Measured outcome
memory and cognitive tests
Operational status
Completed
Results availability
No registry results posted
Governed resultIn 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.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Novartis sponsored HORIZON, with company involvement and author relationships disclosed in the primary reports.
Population / model
7,765 postmenopausal women with osteoporosis; mean age about 73
Design / record
Registered clinical trial · large randomized trial
Measured outcome
vertebral, hip and nonvertebral fractures plus bone density
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultHORIZON reduced vertebral and hip fractures in postmenopausal osteoporosis, with outcome-specific duration and safety limits—not evidence of slower aging.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Novartis sponsored HORIZON, with company involvement and author relationships disclosed in the primary reports.
Population / model
7,765 postmenopausal women with osteoporosis; mean age about 73
Design / record
Registered clinical trial · large randomized trial
Measured outcome
vertebral, hip and nonvertebral fractures plus bone density
Operational status
Completed
Results availability
Peer-reviewed publication linked
Governed resultHORIZON reduced vertebral and hip fractures in postmenopausal osteoporosis, with outcome-specific duration and safety limits—not evidence of slower aging.
Evidence boundaryOperational status describes registry operations. It does not establish scientific quality, safety, efficacy, approval, or benefit.
Relationship contextPublication affiliation for authors of the covered multidimensional-healthspan review and ASPREE healthspan analysis. · Monash institutional support appears in the released ASPREE funding record.
Directory boundaryInclusion, authorship, affiliation, funding, sponsorship, supply, regulator context and editorial coverage are not endorsement, authority, proof, wrongdoing, efficacy, safety or investment merit.
Relationship contextFDA dietary-supplement guidance supplies regulatory context for the covered creatine report. It is not efficacy evidence, product approval or a recommendation.
Directory boundaryInclusion, authorship, affiliation, funding, sponsorship, supply, regulator context and editorial coverage are not endorsement, authority, proof, wrongdoing, efficacy, safety or investment merit.
Relationship contextAuthor of the covered reduced-protein/autophagy report. Authorship and disclosed patent context do not prove influence or validity. · The governed NINA registry projection lists Dr Timothy Sargeant as primary sponsor; sponsorship is not evidence of benefit.
Directory boundaryInclusion, authorship, affiliation, funding, sponsorship, supply, regulator context and editorial coverage are not endorsement, authority, proof, wrongdoing, efficacy, safety or investment merit.
Relationship contextFirst author of the covered systematic review of multidimensional healthspan outcomes. · School of Public Health and Preventive Medicine, Monash University, at publication.
Directory boundaryInclusion, authorship, affiliation, funding, sponsorship, supply, regulator context and editorial coverage are not endorsement, authority, proof, wrongdoing, efficacy, safety or investment merit.
Relationship contextCorresponding author of the covered multidimensional-healthspan review and an author of the covered ASPREE healthspan analysis. · School of Public Health and Preventive Medicine, Monash University, at publication.
Directory boundaryInclusion, authorship, affiliation, funding, sponsorship, supply, regulator context and editorial coverage are not endorsement, authority, proof, wrongdoing, efficacy, safety or investment merit.