Longevity Intervention Evidence Ledger

Every longevity intervention in this list has entered at least one registered human trial search, checked against ClinicalTrials.gov and the primary published literature. One row per intervention: what mechanism it targets, what evidence level backs it, what direction the result pointed, and the trial registry number behind that claim.

Version v2026Q3 · data cutoff 2026-07-27 · updated quarterly · 22 interventions · field completeness checked by an automated verifier before every release

This is a research-literature summary, not medical advice. It does not recommend a dose, a product, or a course of action for anyone. Where the primary literature has not reported an effect, or has not yet reported an effect, this page says so plainly instead of rounding up.
Every row below links to one primary source. The full PDF has every source per intervention, including all counter-evidence and caveats, for offline reading.
Get the full PDF with primary-source citations: $6.99

Rapamycin (sirolimus)

Small human trial safety or feasibility only mTORC1 inhibition

48-week randomised double-blind trial reporting safety and healthspan metrics, not survival

Registered human trials: 36 registered human trials found; the trial referenced here enrolled n=114 · pivotal trial NCT04488601

Primary source: Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results (Aging · 2025)

Counter-evidence on file: 1 source (full list in the PDF)

Dactolisib / RTB101

RCT no effect detected mTORC1 inhibition

The largest registered trial in this ledger; posted results put the primary endpoint at 125/510 on placebo versus 134/511 on drug

Registered human trials: 4 registered human trials found; the trial referenced here enrolled n=1,021 · pivotal trial NCT04668352

Primary source: TORC1 inhibition enhances immune function and reduces infections in the elderly (Science translational medicine · 2018)

Counter-evidence on file: 1 source (full list in the PDF)

Metformin (with resistance training)

RCT adverse effect reported AMPK activation / complex I inhibition

Randomised, double-blind, multicentre: muscle hypertrophy was lower on metformin than on placebo

Registered human trials: 55 registered human trials found; the trial referenced here enrolled n=94 · pivotal trial NCT02308228

Primary source: Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls (Diabetes, obesity & metabolism · 2014)

Counter-evidence on file: 5 sources (full list in the PDF)

Caloric restriction (25%, 2 years)

RCT benefit reported nutrient sensing

Achieved restriction was far below the prescribed 25% (mean about 11.9%); endpoints were predictors of health span, not survival

Registered human trials: 65 registered human trials found; the trial referenced here enrolled n=218 · pivotal trial NCT00427193

Primary source: A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity (The journals of gerontology. Series A, Biological sciences and medical sciences · 2015)

Counter-evidence on file: 2 sources (full list in the PDF)

Dasatinib + quercetin (IPF)

Small human trial safety or feasibility only senescent-cell clearance

First-in-human open-label pilot without a control arm; endpoints were feasibility and physical function, not survival

Registered human trials: 31 registered human trials found; the trial referenced here enrolled n=14 · pivotal trial NCT02874989

Primary source: Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study (EBioMedicine · 2019)

Dasatinib + quercetin (diabetic kidney disease)

Small human trial safety or feasibility only senescent-cell clearance

Open-label; reported changes in senescent-cell markers in adipose and skin tissue

Registered human trials: 22 registered human trials found; the trial referenced here enrolled n=9 · pivotal trial NCT02848131

Primary source: Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease (EBioMedicine · 2019)

Dasatinib + quercetin (Alzheimer's disease)

Small human trial safety or feasibility only senescent-cell clearance

Five participants, open label; the primary endpoints were whether the drugs reach the central nervous system

Registered human trials: 22 registered human trials found; the trial referenced here enrolled n=5 · pivotal trial NCT04063124

Primary source: ClinicalTrials.gov 上 senolytic 相关注册研究总览(用来数真实在跑的人体试验数与样本量量级)

Counter-evidence on file: 1 source (full list in the PDF)

Fisetin

Descriptive running, no published primary result senescent-cell clearance (claimed)

Registered since November 2018 and enrolling by invitation with a listed completion date in 2027; the same compound did not significantly extend mouse lifespan in the ITP

Registered human trials: 13 registered human trials found · pivotal trial NCT03675724

Primary source: ClinicalTrials.gov 上 senolytic 相关注册研究总览(用来数真实在跑的人体试验数与样本量量级)

Counter-evidence on file: 1 source (full list in the PDF)

Nicotinamide riboside (NR)

Small human trial safety or feasibility only NAD+ precursor

Six-week randomised double-blind crossover: well tolerated and blood NAD+ rose; the endpoints were not clinical outcomes

Registered human trials: 31 registered human trials found; the trial referenced here enrolled n=30 · pivotal trial NCT02921659

Primary source: Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults (Nature communications · 2018)

Counter-evidence on file: 1 source (full list in the PDF)

Nicotinamide mononucleotide (NMN)

Descriptive running, no published primary result NAD+ precursor

Many registered studies, but their primary endpoints are biomarkers, physical function or fertility measures rather than lifespan

Registered human trials: No single pivotal trial is assigned here: the 49 registered studies spread across different populations and endpoints, and none has lifespan or mortality as its primary endpoint · pivotal trial no matching NCT registration

Primary source: NAD+ 前体(NR/NMN)注册人体研究

Counter-evidence on file: 1 source (full list in the PDF)

Taurine

Observational no effect detected cysteine-derived metabolite

A six-month human study with biological age as its primary endpoint is registered as completed, while published human work argues against taurine deficiency driving ageing

Registered human trials: 57 registered human trials found · pivotal trial NCT06613542

Primary source: Taurine deficiency as a driver of aging (Science (New York, N.Y.) · 2023)

Counter-evidence on file: 2 sources (full list in the PDF)

Young-donor plasma infusion

Small human trial safety or feasibility only systemic circulating factors

Eighteen participants with safety, tolerability and feasibility endpoints; the FDA has twice publicly warned about paid young-donor plasma infusions

Registered human trials: 22 registered human trials found; the trial referenced here enrolled n=18 · pivotal trial NCT02256306

Primary source: Rejuvenation of aged progenitor cells by exposure to a young systemic environment (Nature · 2005)

Counter-evidence on file: 3 sources (full list in the PDF)

Therapeutic plasma exchange / dilution

Descriptive running, no published primary result removal of circulating factors

Mouse work suggests the active step may be removing old factors rather than adding young ones; no pivotal human trial with an ageing endpoint is registered

Registered human trials: No single pivotal trial is assigned here: the 22 registered studies are mostly neurological and autoimmune indications, and none is a pivotal trial with an ageing endpoint · pivotal trial no matching NCT registration

Primary source: 血浆置换/血浆稀释的注册人体研究

Counter-evidence on file: 1 source (full list in the PDF)

Alpha-ketoglutarate (AKG)

Descriptive running, no published primary result TCA-cycle intermediate

The ITP did not detect a lifespan increase in mice in either of two attempts

Registered human trials: Only six registered studies, none with lifespan or mortality as a primary endpoint, so no pivotal trial is assigned · pivotal trial no matching NCT registration

Primary source: α-酮戊二酸(网红补剂)的注册人体研究

Counter-evidence on file: 1 source (full list in the PDF)

Resveratrol

Animal only no effect detected claimed SIRT1 activation

Resveratrol had no effect in the same ITP cohort, and the claim of direct SIRT1 activation was later attributed to an artefact of the fluorescent substrate

Registered human trials: The 30 registered studies spread across cardiovascular, metabolic and cognitive indications, and none has a lifespan endpoint · pivotal trial no matching NCT registration

Primary source: Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan (Nature · 2003)

Counter-evidence on file: 3 sources (full list in the PDF)

Spermidine (polyamine)

Descriptive safety or feasibility only autophagy induction

A 30-participant pilot with change in cognitive testing as the primary endpoint; the human result is not strong enough to assign a direction

Registered human trials: 3 registered human trials found · pivotal trial NCT02755246

Primary source: Hallmarks of aging: An expanding universe (Cell · 2023)

Urolithin A

Descriptive safety or feasibility only mitophagy

Sixty-six participants with six-minute walking distance as the primary endpoint; the endpoint is physical function, not lifespan

Registered human trials: 7 registered human trials found · pivotal trial NCT03283462

Primary source: Hallmarks of aging: An expanding universe (Cell · 2023)

Canagliflozin

Descriptive running, no published primary result SGLT2 inhibition

In the ITP it extended male but not female mouse lifespan, while only one registered human study uses ageing as a search term (thirty healthy participants)

Registered human trials: 1 registered human trial found · pivotal trial NCT06301529

Primary source: Canagliflozin extends life span in genetically heterogeneous male but not female mice (JCI insight · 2020)

Acarbose

Animal only no registered human study alpha-glucosidase inhibition

One of the largest effects in the ITP, yet no registered human study uses longevity or health span as a search term

Registered human trials: A search on the words longevity and health span returns zero studies. The blank in this row is itself the finding. · pivotal trial no matching NCT registration

Primary source: Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males (Aging cell · 2014)

17-alpha-estradiol

Animal only no registered human study weakly estrogenic agonist

The other largest effect in the ITP has no registered human study at all

Registered human trials: An exact-phrase search for "17-alpha-estradiol" returns zero studies across the whole registry · pivotal trial no matching NCT registration

Primary source: Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males (Aging cell · 2014)

Partial epigenetic reprogramming (OSK)

Animal only no registered human study transcription-factor reprogramming

The direction that has attracted the most industry capital has no registered human study; in mice, over-reprogramming produces teratomas and prematurely terminated reprogramming drives cancer

Registered human trials: A search for Yamanaka factors and partial reprogramming returns zero registered studies · pivotal trial no matching NCT registration

Primary source: In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming (Cell · 2016)

Counter-evidence on file: 2 sources (full list in the PDF)

Studies using epigenetic age as an endpoint

Observational running, no published primary result biomarker (not an intervention)

Clocks are already being used as endpoints on a large scale while their own test-retest reliability is unsettled; three papers making that criticism are listed as counterevidence

Registered human trials: This row is a class of endpoint rather than a single intervention, so there is no pivotal NCT; the total is the number that matters here · pivotal trial no matching NCT registration

Primary source: DNA methylation age of human tissues and cell types (Genome biology · 2013)

Counter-evidence on file: 3 sources (full list in the PDF)