Rapamycin (also called sirolimus) is a drug that inhibits mTOR, a protein complex that senses nutrients and tells cells whether to grow or to recycle their own damaged parts. It was discovered in soil bacteria from Easter Island and is already approved for preventing organ transplant rejection and for coating cardiac stents.
In mice, rapamycin is one of the most consistently replicated lifespan-extending drugs known. The NIH's Interventions Testing Program runs the same experiment at three independent labs. Rapamycin started at 20 months of age (roughly equivalent to a 60-year-old human) increased lifespan by about 9% in males and 14% in females (Harrison et al., 2009). A follow-up dose-response study found the effect grows with dose, reaching 23% in males and 26% in females at the highest dose tested, with females gaining more at every dose (Miller et al., 2014).
Whether any of this transfers to humans is unknown. No trial has tested lifespan in people, and it likely never will directly, since that study would take decades. Human work so far has looked at short-term markers instead:
| Study | Organism | Result | Replicated? |
|---|---|---|---|
| Harrison et al. 2009 | Mice | +9% (M), +14% (F) | Yes, at 3 independent labs |
| Miller et al. 2014 | Mice | +23% (M), +26% (F) at top dose | Yes, dose-response confirmed |
| Mannick et al. 2014 | Humans | About 20% better flu-vaccine response | Not tested on lifespan |
| Moel et al. 2025 (PEARL) | Humans | Safe; primary endpoint missed | Secondary signals, unconfirmed |
The main open problems are dose and schedule. The doses used in mice are high relative to transplant dosing, and continuous mTOR inhibition suppresses the immune system, raises blood lipids, and can cause mouth ulcers and glucose intolerance. Intermittent dosing is the common workaround, on the theory that it separates the beneficial effects from the immunosuppressive ones, but this is not settled.
Does it extend healthy lifespan in humans?
Nothing published answers this. The dog trial is the nearest realistic proxy.
What dose and schedule, if any, gives benefit without immunosuppression?
Weekly and biweekly dosing are used in practice on thin evidence. No dose-ranging trial in healthy people has reported.
Why is the effect larger in female mice?
Seen across several studies but unexplained. Matters for whether human results would differ by sex.
Do PEARL's sex-specific signals reflect real biology or subgroup noise?
The lean-mass and pain results were secondary, subgroup findings in a small trial.
Does it work through autophagy, reduced inflammation, or something else?
Mechanism is assumed more than demonstrated. Affects which biomarkers are worth measuring in trials.
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison et al., Nature, 2009 · Mice
Supports. The original ITP result. Rapamycin was started at 20 months and still extended lifespan at all three testing sites. Replicating across independent labs is what makes this result unusually trustworthy.
Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction
Miller et al., Aging Cell, 2014 · Mice
Supports. Higher doses produced larger effects, and females gained more than males at every dose. A dose-response relationship is one of the stronger signs that an effect is real rather than an artifact.
mTOR inhibition improves immune function in the elderly
Mannick et al., Science Translational Medicine, 2014 · Humans
Mixed. The drug tested was everolimus (RAD001), a rapamycin analog, not rapamycin itself. It improved the antibody response to flu vaccination by about 20% in older adults at well-tolerated doses. Evidence that mTOR inhibition does something measurable to human aging biology, but a vaccine response is a long way from lifespan. The study was sponsored by Novartis.
Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results
Moel et al., Aging (Albany NY), 2025 · Humans (n=114)
Mixed. A 48-week placebo-controlled trial of 5 or 10 mg/week compounded rapamycin in healthy adults aged 50 to 85. Adverse events looked similar to placebo, but the primary endpoint (visceral fat) did not change. Secondary results showed more lean tissue and less pain in women on 10 mg, and better self-reported well-being on 5 mg. It was small, the authors are affiliated with a company that sells rapamycin, and the secondary findings were subgroup analyses, so treat them as hints rather than proof.
Test of Rapamycin in Aging Dogs (TRIAD)
Dog Aging Project · Ongoing · Companion dogs
Pending. A placebo-controlled trial in large pet dogs: one year of weekly dosing, then two years of observation. Enrollment is still being completed, so results are still some way off. Dogs age faster than humans but share our environment, which makes this the closest thing to a real lifespan trial that can report within years rather than decades.