Rapamycin and mTOR Inhibitors in Aging Research
Mouse lifespan results, small human trials and the transplant-drug labels for rapamycin (sirolimus) and related mTOR inhibitors, with the immune and safety limits explained.
Content last updated . This page has not been medically reviewed.
Evidence labels: approved medicine, preclinical (cells/animals only), promising but limited, mixed, insufficient evidence, no good evidence of benefit. A biomarker or lab change is not a health outcome.
Mouse lifespan studies
Label: preclinical (cells/animals only).- In genetically varied mice at three test sites, rapamycin started at 600 days of age (late in life) extended median and maximal lifespan in both sexes; the age at 90% mortality rose by 14% in females and 9% in males. [3]
- At a higher amount, median lifespan rose by 23% in males and 26% in females, and the effect depended on sex and dose. [4]
These are well-run studies, but mice are not people, and the pattern of benefit and harm can differ. See the Interventions Testing Program and claim check: "It extended lifespan in mice".
Human trials
Label overall: promising but limited for immune measures; insufficient evidence for aging outcomes.| Study | Who and how long | Main finding |
|---|---|---|
| Immune response, 2014 (mTOR inhibitor RAD001) | Older volunteers, influenza vaccine | Vaccine response about 20% higher; authors said it was unknown whether this affects aging in humans. [5] |
| Phase 2a, 2018 | 264 older adults, 6 weeks | Fewer self-reported infections over the next year with a low-dose mTOR inhibitor combination. [6] |
| Phase 2b and 3, 2021 | Adults 65 and older, 16 weeks, about 1,000 in phase 3 | Phase 3 did not reduce symptomatic respiratory illness; antiviral gene activity rose. [7] |
| Pilot safety trial, 2018 | 25 healthy adults aged 70 to 95, about 8 weeks | Few side effects (rash, mouth sores, stomach upset); small drops in red blood cell measures. [8] |
| PEARL, 2025 | Healthy adults, 48 weeks, weekly rapamycin vs placebo | Visceral fat (the main outcome) did not change; adverse events were similar across groups. [9] |
| RAPA-EX-01, 2026 | 40 adults aged 65 to 85, 13 weeks with home exercise | Did not improve exercise gains and may have modestly reduced them; more minor adverse events. [10] |
Funding and limits: the 2021 trials were funded by resTORbio, the company developing the drug, and the National Institute on Aging. [7] Most of these trials were small and short, used different drugs and schedules, and tested immune or fitness measures, not survival or disease-free years. The 2018 pilot authors themselves called for larger, longer trials. [8]
Where to go next
Compare with the other leading candidate in metformin vs rapamycin, or see surrogate endpoints and aging biomarkers.Frequently asked questions
Does rapamycin extend lifespan in people?
Not shown. Lifespan extension is established in mice; human trials have been small and short. [3][9]
Is rapamycin approved for aging?
No. Sirolimus is approved for kidney transplant rejection prevention and a rare lung disease. [1]
Did human trials show benefits?
Mixed. Some immune measures improved in older adults, but a larger phase 3 trial did not reduce respiratory illness, and an exercise trial did not show added benefit. [7][10]
What are the main risks?
Suppressed immune defenses with infections and cancers, plus wound healing and blood-fat effects, per the label. [1]
Are these the same as products sold online?
This page covers only the approved drugs and published trials. Proper evidence not found on any marketed product claims.
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
What the drugs are approved for
- Sirolimus is approved in the US to prevent organ rejection in kidney transplant recipients aged 13 and older, and for a rare lung disease (lymphangioleiomyomatosis). [1]
- Everolimus (Zortress) is an mTOR inhibitor immunosuppressant approved to prevent organ rejection in certain kidney and liver transplant recipients. [2]
Aging is not a listed use for either. Label: approved medicine for transplant and rare-disease uses only.
Safety, as stated on the labels
- Immunosuppression. The sirolimus label warns that increased susceptibility to infection and possible development of lymphoma and other malignancies may result from immunosuppression. [1]
- Other label risks. The label lists fluid accumulation, impaired wound healing, high blood fats and lung inflammation among its warnings. [1]
- Everolimus carries a boxed warning covering malignancies and serious infections, among others. [2]
- Older adults. The sirolimus label notes that its studies did not include enough people aged 65 and over to know if they respond differently. [1]
Anyone taking other medicines, with infections, diabetes or planned surgery faces extra considerations; discuss with your prescriber. See longevity compounds and medication interactions and off-label prescribing for longevity.
References
- Sirolimus tablets, US prescribing information (DailyMed). Read 2026-10-22.
- Zortress (everolimus) tablets, US prescribing information (DailyMed). Read 2026-10-22.
- Harrison DE et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009. Read 2026-10-22.
- Miller RA et al. Rapamycin-mediated lifespan increase in mice is dose and sex dependent. Aging Cell 2014. Read 2026-10-22.
- Mannick JB et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med 2014. Read 2026-10-22.
- Mannick JB et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med 2018. Read 2026-10-22.
- Mannick JB et al. mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 trials. Lancet Healthy Longev 2021. Read 2026-10-22.
- Kraig E et al. A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort. Exp Gerontol 2018. Read 2026-10-22.
- Moel M et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging 2025. Read 2026-10-22.
- RAPA-EX-01: exercise and weekly sirolimus (rapamycin) in older adults, randomised placebo-controlled trial. J Cachexia Sarcopenia Muscle 2026. Read 2026-10-22.