Wellness & longevity interventions.

Sirolimus · Rapamune

An mTOR inhibitor that shifts cells from growth toward maintenance and stress resistance. It reliably extends lifespan in genetically heterogeneous mice; no human trial has shown a lifespan or hard-outcome benefit.

• Inhibits mTORC1, reducing S6K1 and 4E-BP1 signalling
• Induces autophagy through ULK1 de-repression
• Most reproducible pharmacological lifespan extension in mice (NIA ITP)
• Human work so far measures safety and healthspan surrogates, not lifespan

Status: Approved as an immunosuppressant; longevity use is off-label with only pilot human safety and biomarker data.

Glucophage · TAME candidate

The leading repurposing candidate for an ageing-outcome trial. Its diabetes evidence is overwhelming; its anti-ageing evidence is observational and contested.

• AMPK activation with downstream reduction in mTORC1 signalling
• Mild complex-I inhibition lowering hepatic gluconeogenesis
• UK CPRD cohort suggested mortality comparable to non-diabetic controls
• TAME proposes multimorbidity delay as a composite endpoint

Status: Approved worldwide for type 2 diabetes. The geroprotective claim rests on observational data; the dedicated TAME trial is not complete.

Precose · Glucobay

A carbohydrate-absorption blocker that produces one of the most reproducible lifespan effects in the NIA Interventions Testing Program, with a strong male bias.

• Blocks intestinal alpha-glucosidase, blunting glucose and insulin spikes
• Extends median lifespan in male UM-HET3 mice, less so in females
• Additive lifespan benefit when combined with rapamycin
• Improves late-life physical function and cardiac markers in mice

Status: Approved as an oral antidiabetic. No human ageing-outcome trial exists.

D+Q senolytic combination

The first senolytic regimen taken into humans. Small trials show measurable senescent-cell clearance and organ-specific signals; no large outcome trial has reported.

• Intermittent hit-and-run dosing rather than continuous exposure
• Reduced senescent cell burden in adipose tissue and skin in diabetic kidney disease
• Improved physical function signals in idiopathic pulmonary fibrosis pilots
• Phase 1 Alzheimer's trial showed CNS penetration and tolerability

Status: Dasatinib is an approved cancer drug; the senolytic combination is investigational with early-phase human data only.

HMG-CoA reductase inhibitors

The largest randomised evidence base of any drug considered here. Their longevity relevance runs through cardiovascular event prevention rather than ageing biology.

• Inhibit HMG-CoA reductase, the rate-limiting step of hepatic cholesterol synthesis
• Primary-prevention meta-analyses show reduced cardiovascular events
• All-cause mortality benefit is smaller and debated in lower-risk groups
• Cardiovascular mortality reduction is a major real-world contributor to lifespan

Status: Approved worldwide for lipid lowering and cardiovascular risk reduction; not an approved ageing drug.

Nicotinamide mononucleotide

An NAD+ precursor with reliable biomarker effects in placebo-controlled trials. Whether raising NAD+ changes ageing outcomes in people is unproven.

• Direct NAD+ precursor supporting sirtuin and PARP activity
• Raises whole-blood NAD+ dose-dependently in healthy adults
• Improved muscle insulin sensitivity in prediabetic women in one RCT
• No long-term clinical outcome data

Status: Sold as a dietary supplement with ongoing US regulatory disputes. Trials measure biomarkers, not hard outcomes.

NR · Niagen

The best-studied NAD+ precursor in humans. It moves the biomarker it targets but has not yet improved a functional endpoint, and it failed to extend mouse lifespan.

• NAD+ precursor metabolised via NRK1/2 kinases
• Safely and reliably raises blood NAD+ in older adults
• Did not extend lifespan in NIA ITP mouse studies
• Cognitive outcomes in MCI trials have been mixed or negative

Status: Supplement, not an approved drug. Mouse lifespan data are explicitly negative and cognitive trials are mixed to null.

trans-resveratrol

A polyphenol whose sirtuin-activation story did not survive scrutiny. Human trials support small cardiometabolic effects rather than a longevity mechanism.

• Originally proposed as a SIRT1 activator mimicking caloric restriction
• Meta-analyses show modest fasting glucose and HbA1c reductions
• Lipid effects are inconsistent across trials
• Poor oral bioavailability limits translation from animal data

Status: Unregulated supplement. Meta-analyses show modest metabolic effects only; no longevity outcome data.

Wheat-germ polyamine

A dietary polyamine that switches on autophagy, one arm of the caloric-restriction response. Cohort mortality data and small cognition RCTs are encouraging but not definitive.

• Induces autophagy partly via EP300 acetyltransferase inhibition
• Higher dietary intake associated with lower mortality in the Bruneck cohort
• Improved memory in older adults at risk of dementia in an RCT
• Found in wheat germ, aged cheese and legumes

Status: Food-derived supplement. Mortality evidence is observational; cognition trials are small.

Senolytic flavonoid

A dietary flavonoid with senolytic activity in cell and mouse models. Human evidence remains preliminary and largely uncontrolled.

• Identified as a senolytic in high-throughput screens
• Preferentially clears senescent cells and reduces SASP signalling in mice
• A small open-label pilot reported reduced methylation age
• Phase 2 trial in cancer survivors is ongoing without results

Status: Supplement. Only pilot and feasibility human studies exist; no completed efficacy RCT for ageing endpoints.

Mitopure · ellagitannin metabolite

One of the few supplements with repeated placebo-controlled human data showing target engagement and modest muscle-function benefit.

• Gut-microbiome metabolite of pomegranate and walnut ellagitannins
• Activates mitophagy, clearing damaged mitochondria
• Improved muscle endurance and mitochondrial biomarkers in RCTs
• Lowered plasma acylcarnitines and CRP

Status: Supplement with several placebo-controlled human trials on mitochondrial and muscle endpoints.

AKG · Ca-AKG · Rejuvant

A metabolite with plausible epigenetic mechanisms and eye-catching but methodologically weak human data. Treat the biological-age claim as unconfirmed.

• TCA-cycle intermediate and cofactor for TET and JmjC dioxygenases
• Links metabolic state to epigenetic regulation
• Uncontrolled cohort reported large methylation-age reductions
• ABLE randomised trial is registered and running

Status: Supplement. The headline biological-age result comes from an uncontrolled, commercially linked cohort; a randomised trial is underway.

2-aminoethanesulfonic acid

A semi-essential amino acid proposed as a driver, not just a marker, of ageing. The 2023 Science paper is the reference point; a human outcome trial is still missing.

• Circulating taurine declines with age in mice, monkeys and humans
• Supplementation extended lifespan in mice and worms
• Improved bone, muscle and metabolic markers in monkeys
• Human component of the landmark study is observational

Status: Cheap over-the-counter amino acid. Cross-species animal data are strong; human evidence is associational.

Glycine + N-acetylcysteine

A cheap two-ingredient approach to correcting the age-related glutathione deficit, with promising but not yet widely replicated randomised evidence.

• Supplies both precursors needed to restore intracellular glutathione
• Reduced oxidative stress and improved mitochondrial fuel oxidation
• Pilot RCT reported gains in strength, gait speed and cognition
• Independent trial confirmed redox effects with narrower functional claims

Status: Both components are widely available. Two positive RCTs come from one group; independent replication is limited.

EPA/DHA · DO-HEALTH

Tested rigorously as a healthy-ageing intervention in DO-HEALTH. The honest reading is null primary outcomes with interesting secondary signals.

• Modulates inflammatory eicosanoid balance and membrane composition
• DO-HEALTH used a 2x2x2 factorial design in adults aged 70 and over
• Primary outcomes were not significantly improved by omega-3 alone
• Secondary analyses suggested reduced invasive cancer in combination arms

Status: Widely available supplement. In DO-HEALTH the pre-specified primary healthy-ageing outcomes were null.

Cholecalciferol

The clearest example of a supplement whose observational promise did not survive large randomised testing outside of deficiency states.

• Acts through the nuclear vitamin D receptor on hundreds of genes
• VITAL (n=25,871) found no reduction in major cardiovascular events or invasive cancer
• Meta-analysis suggests a small cancer-mortality reduction only
• Benefit is plausibly restricted to people who are deficient

Status: Nutrient supplement; prescription doses treat diagnosed deficiency. Large RCTs are null for all-cause mortality in replete populations.

Creatine

The most evidence-backed sports supplement, and increasingly a geriatric one: combined with resistance training it consistently adds strength and lean mass in older adults.

• Buffers ATP regeneration through the phosphocreatine shuttle
• Meta-analyses show added strength and lean mass when combined with resistance training
• Benefit is much weaker without structured training
• Directly relevant to sarcopenia prevention in older adults

Status: Well-characterised over-the-counter supplement with a strong safety record at standard doses.

CR · CALERIE 2

The oldest and most conserved anti-ageing intervention. In humans the rigorous evidence is biomarker-level: ageing pace slowed, lifespan untested.

• McCay's 1935 rodent study founded the whole field
• CALERIE 2 tested roughly 15% restriction in non-obese adults for two years
• Slowed the DunedinPACE epigenetic pace-of-ageing measure
• Reduced senescence biomarkers and preserved telomere length

Status: Behavioural intervention. CALERIE measured biomarkers over two years; no human lifespan trial is feasible.

TRE · 16:8 intermittent fasting

A popular eating pattern whose benefit appears to come mostly from eating less, not from the window itself.

• Aligns intake with circadian metabolic rhythms
• Modest weight loss in 12-week trials of overweight adults
• Isocaloric trials show no advantage over standard eating patterns
• Early-window eating may hold a small metabolic edge over late windows

Status: Behavioural pattern. Effects largely disappear when calories are matched.

Aerobic and resistance training · LIFE · Generation 100

The intervention with the strongest causal human evidence for preserving function in later life, and a useful benchmark for judging every supplement on this page.

• LIFE (n=1,635) reduced major mobility disability versus health education
• Generation 100 (n=1,567) found no significant all-cause mortality reduction over five years
• Generation 100 secondary analyses showed improved cardiovascular risk profile
• Improves mitochondrial function, muscle mass and vascular health

Status: Freely available. Two of the largest ageing RCTs show functional benefit; mortality benefit was not demonstrated in already-active cohorts.

Finnish sauna · KIHD cohort

Repeated passive heat exposure looks like a mild cardiovascular conditioning stimulus. The evidence is a strong dose-response cohort signal, not proof of causation.

• Heat exposure induces heat-shock proteins and improves endothelial function
• 4-7 sessions per week associated with lower sudden cardiac death risk
• Dose-response by both frequency and session length
• Associations persist in men and women in a second cohort

Status: No randomised mortality trial exists; all findings are observational and from Finnish cohorts.

Habitual sleep · U-shaped mortality curve

Sleep duration shows one of the most consistent U-shaped mortality associations in epidemiology, though causality cannot be established by randomisation.

• Both short and long habitual sleep associate with higher all-cause mortality
• Non-linear meta-regression of 40 cohorts refined the U-shaped curve
• A 2025 meta-analysis put the excess risk at 14-34%
• Mechanisms proposed include inflammation and metabolic dysregulation

Status: Not randomisable. Reverse causation, where illness drives long sleep, is a persistent confounder.

17aE2 · non-feminising estrogen

A non-feminising estrogen stereoisomer with a striking male-specific lifespan effect in mice, driven by hypothalamic and metabolic changes.

• Extends median lifespan in male but not female UM-HET3 mice
• Weakly estrogenic, without classical uterotrophic activity
• Reduces visceral adiposity and improves insulin sensitivity in aged males
• Effect depends on intact gonadal hormone signalling

Status: Research compound only; no human clinical development.

HRT · MHT · WHI

The canonical case study in why observational hormone-ageing associations must be randomised. Interpretation of subgroups remains actively debated.

• WHI combined estrogen plus progestin arm stopped early for excess breast cancer, stroke and CHD
• Estrogen-alone arm showed a more favourable profile in women with prior hysterectomy
• The timing hypothesis suggests different risk-benefit near menopause onset
• WHI reshaped global prescribing after 2002

Status: Approved for menopausal symptoms; longevity use is not an approved indication and risk-benefit depends heavily on age at initiation.

Semaglutide · Wegovy · SELECT

The trial that moved GLP-1 agonists from metabolic drugs to candidate geroprotectors, by showing hard cardiovascular outcome benefit in people without diabetes.

• SELECT (n=17,604) cut major adverse cardiovascular events by about 20%
• First cardiovascular benefit shown independent of a diabetes diagnosis
• Combines weight loss with possible direct vascular and anti-inflammatory effects
• No lifespan or multimorbidity-delay endpoint tested yet

Status: Approved for obesity and diabetes. Cardiovascular outcome benefit is established; no ageing endpoint has been tested.

HBOT

An established medical procedure being repurposed for ageing on the strength of one small, unblinded telomere study. Treat as preliminary.

• Repeated hyperoxia followed by relative hypoxia may act as a hormetic stimulus
• One prospective trial reported increased leukocyte telomere length after ~60 sessions
• The same trial reported fewer senescent T cells
• Single-centre, non-blinded, no independent replication

Status: Approved for decompression sickness and wound care; anti-ageing use is off-label and rests on a single small trial.

Plasmapheresis · plasma dilution

An invasive procedure with a plausible mechanism and small, mostly biomarker-level human evidence from a handful of affiliated groups.

• Dilutes accumulated circulating pro-ageing and inflammatory factors
• Rationale drawn from heterochronic parabiosis and blood-exchange studies
• Small studies report reduced methylation-based biological age
• No large trial with clinical rather than biomarker endpoints

Status: Not approved for ageing indications. Carries real procedural risks including infection, clotting and reactions to replacement fluid.