7 Drugs. 30,000 Mice. 20 Years. The Only Longevity Compounds With Real Evidence.
The longevity supplement market hit $85 billion in 2025. Most of it is noise.
The NIA Interventions Testing Program has been quietly running the most rigorous longevity drug trial in history since 2004. Three independent labs. Genetically diverse mice (not inbred clones). Results published regardless of outcome. No cherry-picking.
They've tested 54 compounds. The majority did nothing. Seven stood out. One combination beat everything.
I've compiled every compound, every cohort, every result into a public database. This article is the summary. Bookmark it.
THE PROGRAM THAT SETTLES ARGUMENTS
Most longevity studies use inbred mice at a single lab. Results often don't replicate.
The ITP was designed to fix that. Every compound is tested simultaneously at Jackson Laboratory in Maine, the University of Michigan, and UT Health San Antonio. The mice are UM-HET3, a four-way cross that produces genetic diversity comparable to a human population. Each test uses roughly 300 mice per compound (150 per sex). And every result gets published, positive or negative.
This is the closest thing aging research has to a clinical trial. When a compound works in the ITP, it works for real.
Over 20 years, 54 agents have been tested. Here are the seven that extended lifespan, ranked by their strongest documented effect.
Ranked: The top drugs with proven evidence to extend lifespan.
1: RAPAMYCIN + ACARBOSE (THE COMBINATION THAT BEAT EVERYTHING)
Median lifespan increase: +37% in males, +28% in females (started at 9 months)
Late start (16 months): +14% males, +12% females
Both median AND maximum lifespan extended in both sexes
This is the largest effect the ITP has ever documented. Rapamycin suppresses mTOR (the growth-signaling pathway). Acarbose slows glucose absorption. Together, they hit two different aging mechanisms simultaneously.
The oncology parallel writes itself. Cancer medicine abandoned single agents decades ago. Combination protocols that hit multiple targets simultaneously produce better results. This is the first strong evidence that the same principle applies to aging.
Started at 9 months (roughly equivalent to a 30-year-old human), the combination produced a 37% median lifespan increase in males. Even starting at 16 months (roughly 55 in human years), it still produced double-digit extensions in both sexes.
Source: Strong et al., Aging Cell, 2022.
2: RAPAMYCIN ALONE (THE MOST REPLICATED LONGEVITY DRUG IN HISTORY)
Best result: +28% in females, +22% in males (42 ppm, started at 9 months)
Late start (20 months): +20% males, +13% females
Tested across 5 separate cohorts from 2005-2015
Rapamycin is the single most consistent lifespan extender ever tested. It works at multiple doses, at multiple ages, in both sexes, across every site. No other compound comes close to this replication record.
It's also the only compound in the ITP that works BETTER in females than in males. At the standard 14 ppm dose started at 9 months: +22% in females versus +10% in males. At the low 4.7 ppm dose: +17% in females, not significant in males.
Every other successful compound in the ITP shows the opposite pattern. This makes rapamycin unique in the longevity pharmacology literature.
It was originally developed as an immunosuppressant for organ transplants. Its anti-aging effects were discovered accidentally when transplant patients showed unexpected health improvements.
Source: Harrison et al. 2009, Miller et al. 2011, Miller et al. 2014.
3: ACARBOSE (THE DIABETES DRUG WITH A 22% EFFECT)
Best result: +22% median in males (1000 ppm, started at 4 months)
Females: +5% median (consistent across doses)
Also extended maximum lifespan: +11% in males
Acarbose is a Type 2 diabetes drug that blocks alpha-glucosidase, the enzyme that breaks down complex carbohydrates. It slows sugar absorption, blunts post-meal glucose spikes, and reduces insulin signaling.
The sex difference is dramatic: 22% in males versus 5% in females. The ITP tested acarbose at three different concentrations (400, 1000, and 2500 ppm). All doses extended male lifespan. The effect held even when started at 16 months of age.
Acarbose is generic, cheap, and has been used safely in humans for decades. It's arguably the most practical longevity drug candidate on this list.
Source: Strong et al., 2016; Harrison et al., 2014.
4: CAPTOPRIL (THE BLOOD PRESSURE DRUG NOBODY EXPECTED)
Median lifespan increase: +14% males, +5% females
Maximum lifespan: +7% males, +8% females
Captopril is an ACE inhibitor prescribed for high blood pressure. It blocks the conversion of angiotensin I to angiotensin II, reducing blood pressure and vascular inflammation.
Its inclusion on this list surprised the aging field. ACE inhibitors weren't considered longevity candidates. Captopril's results suggest that the renin-angiotensin system plays a larger role in aging than previously thought.
Captopril is one of the few compounds that extended both median AND maximum lifespan in both sexes. The male median effect (+14%) is clinically meaningful. The female benefit is smaller but still statistically significant.
Source: Strong et al., Aging Cell, 2022.
5: 17-ALPHA-ESTRADIOL (THE WEAK ESTROGEN, MALES ONLY)
Best result: +19% median in males, +12% maximum (14 ppm, 10 months)
Females: No effect at any dose
Works whether started young or in late middle age
17-alpha-estradiol is a naturally occurring weak estrogen. Unlike 17-beta-estradiol (the primary female sex hormone), 17-alpha-estradiol has very low feminizing activity. Its lifespan effects appear to work through altered metabolism and reduced age-related inflammation.
The sex specificity is complete: 19% in males, literally zero in females. This is consistent across two separate ITP cohorts. And it works whether you start treatment at 10 months or later.
The mechanism isn't fully understood. It reduces fat mass, improves glucose metabolism, and lowers inflammation. But why it only benefits males remains an open question.
Source: Harrison et al., 2014; Strong et al., 2016.
A stark sex bias exists in longevity science: almost all proven lifespan-extending drugs work primarily in males—with one major exception.
6: CANAGLIFLOZIN (THE SGLT2 INHIBITOR)
Best result: +14% median in males (180 ppm, 7 months)
Maximum lifespan: +9% in males
Females: No benefit (and possibly harmful at late start)
Canagliflozin blocks glucose reabsorption in the kidneys. You literally urinate out excess sugar. It's prescribed for Type 2 diabetes and has cardiovascular benefits in humans.
In the ITP, it extended male lifespan by 14% at the standard dose. At a late start (16 months), males still showed +13.8%. But in females, the late-start group actually showed a significant reduction in lifespan (-6.1%). Blood levels of canagliflozin were 20-fold higher in aged females, suggesting potential toxicity.
This is a cautionary reminder: sex-specific drug responses aren't just about efficacy. They can flip from beneficial to harmful.
Source: Miller et al., 2020; Harrison et al., 2024.
#7: GLYCINE (THE ONLY COMPOUND THAT WORKS EQUALLY IN BOTH SEXES)
Median lifespan increase: +6% males, +4% females
Maximum lifespan: +5% males
Glycine is the simplest amino acid. It's cheap, widely available, and has an excellent safety profile. It's also the only compound in the ITP that extended lifespan in both males AND females with roughly equal effect sizes.
The proposed mechanism: glycine mitigates the harmful effects of excess methionine in the diet. High methionine intake accelerates aging. Glycine acts as a buffer.
A 6% median increase is modest compared to rapamycin. But glycine's sex-equitable effect, combined with its safety and availability, makes it uniquely interesting for translation.
Source: Miller et al., 2019.
WHAT PEOPLE SPEND BILLIONS ON (THAT DIDN'T WORK)
The ITP has tested many popular supplements and drugs. These showed no significant lifespan extension:
Resveratrol: tested at two doses (300 and 1200 ppm). No significant effect in either sex. Three separate cohorts.
Nicotinamide riboside (NR): No effect. Males -3%, females 0%. Both non-significant.
Fisetin: Marketed as a senolytic. No effect in the ITP. -5% in males (non-significant). Tested both continuously and in cycling doses.
Fish oil: No effect at either dose (15,000 or 50,000 ppm).
Metformin: The most surprising failure. Despite enormous hype and the TAME clinical trial, metformin at 1000 ppm produced +7% in males and 0% in females, both non-significant. However, metformin + rapamycin together worked well (+23% both sexes).
Curcumin: No effect. Green tea extract: No effect. Alpha-ketoglutarate: No effect.
The pattern: most popular anti-aging supplements have been tested by the ITP and failed.
Evidence vs. Marketing Hype: Over 20 years of rigorous testing, the ITP found only 7 specific compounds extend lifespan in mice, while most popular anti-aging supplements had no significant effect.
THE SEX PROBLEM LONGEVITY MEDICINE HASN'T SOLVED
Of the 13 individual compounds that extended lifespan in the ITP, 12 worked primarily or exclusively in males. Rapamycin is the sole exception.
This isn't a quirk. It's a structural pattern. And it raises a genuine translational concern: if most longevity drugs work better in males, what does that mean for the half of the human population that's female?
The Jiang et al. 2025 review of 20 years of ITP data makes this the central thesis. The program tested every compound in both sexes from the start. The sex bias isn't an artifact of study design. It's biology.
Glycine is the only compound with roughly equal effects. Captopril works in both sexes, though more strongly in males. Everything else skews male.
Combination therapies may hold the answer. Rapamycin + acarbose worked in both sexes. Rapamycin + metformin worked equally in both. Perhaps combinations that pair a male-biased compound with a female-responsive compound could close the gap.
WHAT THIS MEANS FOR HUMANS
These are mouse results. That needs saying clearly.
No ITP compound has been tested in a human longevity trial with lifespan as the endpoint. The TAME trial (Testing Against Metformin in the Elderly) is the closest attempt, and it targets age-related disease incidence, not lifespan directly.
Rapamycin human trials exist for immune function (resTORbio) and ovarian aging (Columbia VIBRANT). Neither is a lifespan trial.
But three things translate from the ITP data with confidence:
First, pharmacological lifespan extension is real and reproducible. This isn't theoretical. It works in the most rigorous animal model we have.
Second, combination protocols outperform single agents. The rapamycin + acarbose result is the strongest in ITP history.
Third, sex matters. Any human longevity protocol that ignores biological sex is flying blind.
THE FULL DATABASE
We've compiled every ITP compound, every cohort, every result into a public spreadsheet. Median and maximum lifespan data. Male and female effects. P-values. Doses. Ages at treatment initiation. Source citations.
It's the most complete public catalog of ITP results that exists.
The data tells a clear story. Of 54 compounds tested by the gold standard longevity program, seven extended life. Most popular supplements failed. Combinations beat single drugs. And nearly everything worked better in males.
The $85 billion anti-aging market would look very different if it followed this evidence.