Frontier · Not clinical advice

Experimental research with promise

A curated map of longevity interventions that are scientifically credible and showing early signal — but are not yet established practice. Each entry summarises the mechanism, the strongest published evidence, and the caveats a careful reader should hold in mind.

Read this before getting excited.

"Promising" is not "proven." Most interventions on this page have either no human outcome trials or only small, short ones. Animal lifespan results often fail to translate. Use this as a literature map, not a protocol — and never start prescription-grade interventions outside a supervised trial.

Partial epigenetic reprogramming (OSK / OSKM)

Transient expression of Yamanaka factors to roll back the epigenetic age of cells without losing identity.

Strong mechanismPreclinical

Mechanism: Cyclic or short-pulse OSK delivery resets DNA-methylation patterns, recovers youthful transcriptional programs, and restores regenerative capacity in aged tissues.
Best evidence: Restored vision in aged and glaucomatous mice via AAV-OSK in retinal ganglion cells (Lu, Sinclair et al., Nature 2020). Whole-body cyclic OSKM extends lifespan in progeroid mice and improves multiple tissues in naturally aged mice (Ocampo et al., Cell 2016; Browder et al., Nature Aging 2022). Chemical reprogramming cocktails reproduce some effects without genetic delivery (Yang et al., Aging 2023).
Caveats: Teratoma risk if OSKM is sustained; delivery, dosing, and tissue specificity in humans are unsolved. No human efficacy data.

Senolytics — Dasatinib + Quercetin, Fisetin

Intermittent drug pulses that selectively kill senescent ('zombie') cells driving inflammaging.

Mixed human dataPhase 2/3

Mechanism: Disable pro-survival pathways (BCL-2/BCL-xL, PI3K, p53/p21) that senescent cells depend on, allowing apoptosis without harming healthy cells.
Best evidence: D+Q clears senescent cells and improves physical function in mice (Zhu et al., Aging Cell 2015). Small open-label human trials show reduced senescent-cell burden in adipose tissue and skin in diabetic kidney disease (Hickson et al., EBioMedicine 2019) and improved gait speed in IPF (Justice et al., EBioMedicine 2019). Fisetin extends healthspan in mice (Yousefzadeh et al., EBioMedicine 2018); large RCTs (e.g. Mayo AFFIRM-LITE) ongoing.
Caveats: Most positive trials are tiny and unblinded; dasatinib has real toxicity (cytopenias, effusions). Optimal cadence unknown.

Rapamycin and rapalogs (mTOR inhibition)

The most reproducible lifespan-extending drug across model organisms; cautiously tested at low intermittent doses in humans and dogs.

Replicated in animalsPhase 2/3

Mechanism: Inhibits mTORC1, suppressing anabolic signalling, enhancing autophagy, and mimicking some effects of caloric restriction.
Best evidence: Extends median and maximum lifespan in mice even when started in middle age (Harrison et al., Nature 2009; ITP replications). RTB101 improved respiratory infection rates in elderly (Mannick et al., Sci Transl Med 2018; Lancet HL 2021 mixed). PEARL human RCT showed safety and some body-composition signals (Kaeberlein, 2023). Dog Aging Project TRIAD trial in large breeds underway.
Caveats: Chronic high-dose rapamycin causes glucose intolerance, mouth ulcers, dyslipidemia, and immunosuppression. No human longevity endpoint trial.

NAD+ precursors — NMN, NR

Oral precursors that raise tissue NAD+ to support sirtuin and PARP activity.

Mixed human dataPhase 1/2

Mechanism: NMN and NR feed the salvage pathway, restoring NAD+ levels that decline with age and supporting mitochondrial function and DNA-repair signalling.
Best evidence: Robust mouse data on metabolic and vascular benefits (Mills et al., Cell Metab 2016; Yoshino et al., Cell Metab 2021 — improved insulin sensitivity in prediabetic women). Multiple small human RCTs show NAD+ does rise; functional endpoints (strength, VO2max, walking) are inconsistent.
Caveats: Long-term safety unclear; theoretical concern about feeding NAD+ to occult tumours. Hype far ahead of human evidence.

Plasma factors — dilution, young plasma fractions, GDF11

Replacing or diluting circulating factors to rejuvenate aged tissues.

Early signalPhase 1/2

Mechanism: Heterochronic parabiosis suggested young blood carries pro-youthful factors and old blood carries pro-aging ones; subsequent work points more to dilution of inhibitory factors than to specific 'young' molecules.
Best evidence: Neutral blood exchange (replacing plasma with albumin/saline) improved muscle, liver, and brain markers in aged mice (Mehdipour et al., Aging 2020; Conboy lab). Therapeutic plasma exchange in humans is in early trials for aging biomarkers and Alzheimer's (AMBAR). GDF11 results remain contested.
Caveats: Young-plasma infusion clinics oversold a thin evidence base (FDA warned in 2019). Mechanism is dilution, not magic factors.

Taurine supplementation

Conditionally essential amino acid that declines with age and extended healthspan in multiple species.

Replicated in animalsPreclinical

Mechanism: Modulates mitochondrial function, calcium handling, antioxidant defences, and reduces cellular senescence markers.
Best evidence: Singh et al., Science 2023: taurine supplementation extended median lifespan ~10–12% in mice and improved healthspan in monkeys; human cross-sectional data correlates higher taurine with better metabolic health.
Caveats: No human RCT for longevity endpoints. Causality in humans not established; baseline taurine status varies.

Urolithin A

Gut-microbiome metabolite of ellagitannins (pomegranate, walnuts) that induces mitophagy.

Early signalPhase 2/3

Mechanism: Selectively triggers removal of damaged mitochondria, improving mitochondrial quality and muscle function.
Best evidence: Extends lifespan in C. elegans and improves muscle function in aged mice (Ryu et al., Nat Med 2016). Human RCTs (Andreux et al., Nat Metab 2019; Liu et al., JAMA Netw Open 2022) show improved muscle endurance and mitochondrial gene expression in older adults.
Caveats: Effect sizes are modest; only ~40% of people produce urolithin A from food. Long-term outcomes unknown.

Spermidine

Polyamine that induces autophagy; dietary intake associates with lower mortality.

Early signalPhase 1/2

Mechanism: Activates autophagy independent of caloric restriction, improves cardiac and neuronal function in aged animals.
Best evidence: Extends lifespan in yeast, flies, worms, and mice (Eisenberg et al., Nat Med 2016). Observational human data link higher dietary spermidine to lower all-cause and cardiovascular mortality. Small trials suggest cognitive benefit in mild cognitive impairment (SmartAge).
Caveats: Confirmatory RCTs are small and short. Optimal source (food vs. supplement) and dose unsettled.

Gene therapies — telomerase (TERT), follistatin, Klotho

AAV-delivered single-gene therapies that target a specific aging axis.

Strong mechanismPreclinical

Mechanism: TERT lengthens telomeres in somatic cells; follistatin antagonises myostatin to build muscle; Klotho supports kidney, vascular, and cognitive function.
Best evidence: AAV9-TERT extended median lifespan ~24% in adult mice without raising cancer (Bernardes de Jesus et al., EMBO Mol Med 2012). Follistatin and Klotho gene therapies improve muscle and metabolic markers in mice. Libella and Minicircle have run small unregulated human cohorts; scientific community considers these data uninterpretable.
Caveats: Off-shore unregulated trials are not credible evidence. Insertional mutagenesis and cancer risk remain open questions.

GLP-1 receptor agonists as geroprotectors

Semaglutide / tirzepatide may have aging-relevant benefits beyond weight and glucose.

Mixed human dataPhase 2/3

Mechanism: Improves cardiometabolic risk, reduces low-grade inflammation, and shows neuroprotective and renoprotective signals.
Best evidence: SELECT (NEJM 2023) reduced MACE 20% in overweight non-diabetics; FLOW reduced kidney disease progression; emerging signals in MASH, sleep apnoea, and dementia. Repurposing for healthspan is now a serious hypothesis.
Caveats: Long-term effects on muscle, bone, and frailty in older adults need careful study. Not yet a proven longevity drug.

17α-estradiol

Non-feminising estrogen analogue that extends male mouse lifespan in NIH ITP.

Replicated in animalsPreclinical

Mechanism: Acts on hypothalamic and hepatic targets to improve insulin sensitivity and reduce inflammation, without classical feminising effects.
Best evidence: Reproducible male-specific lifespan extension in NIA Interventions Testing Program (Strong et al., Aging Cell 2016, 2020). Mechanistic work points to mTORC2 and androgen-pathway interactions.
Caveats: Female mice did not benefit. No human data. Unclear whether it would translate.

Mitochondrial transplantation & exosome therapies

Transferring functional mitochondria or young-cell-derived vesicles to aged tissues.

Early signalPreclinical

Mechanism: Donor mitochondria are taken up by recipient cells; young exosomes carry RNAs and proteins that may reprogram aged cells.
Best evidence: Established clinical use for paediatric cardiac ischaemia (McCully, Boston Children's). Aging-focused exosome work (e.g. e5 by Horvath) shows reductions in epigenetic age in rats.
Caveats: Aging applications are very early. Manufacturing, dosing, and durability unsolved.

How to read this page

Strong mechanism — beautiful biology, sparse human evidence. Watch the trials.
Replicated in animals — convergent results across species; human translation pending.
Mixed human data — some trials positive, others null; signal is real but heterogeneous.
Early signal — small, short, or surrogate-endpoint trials only.

For graded individual claims, see the Evidence Grader. For Sinclair's information theory specifically, see Module 09.