Rapamycin is an FDA-approved immunosuppressant that inhibits mTOR signaling. It has extended lifespan in several mouse experiments, including a three-site study in genetically heterogeneous mice. Human trials have not shown that it extends life. The 48-week PEARL trial found no significant effect on its primary endpoint, visceral adiposity, while reporting exploratory improvements in lean tissue mass and pain in a small subgroup of women. A separate 2026 trial found that weekly sirolimus did not improve exercise gains in older adults and may have modestly attenuated them. Rapamycin, under the generic name sirolimus, was first approved in the United States in 1999 to prevent organ rejection after kidney transplantation. FDA later approved it for lymphangioleiomyomatosis in 2015. Neither approval covers aging, longevity, or prevention of age-related disease. The prescribing information carries a boxed warning about immunosuppression, infection, and malignancy risk.
Macrolide mTOR inhibitor and prescription immunosuppressant; not a peptide
Rapamycin (sirolimus)
Rapamycin extends lifespan in mice, but human longevity claims remain unproven. Exploratory human trials have measured safety and healthspan proxies, with a null primary endpoint in PEARL and no exercise benefit in RAPA-EX-01.
Evidence snapshot
Regulatory: FDA approval is indication-specific: renal-transplant rejection prophylaxis and LAM. No anti-aging indication exists.
Human aging evidence: PEARL was a 48-week randomized trial, but its primary endpoint, visceral adipose tissue, was null. Positive findings were secondary and subgroup signals.
Human exercise evidence: RAPA-EX-01 found no enhancement of functional gains and sensitivity analyses suggested possible attenuation.
Animal evidence: late-life rapamycin extended lifespan in genetically heterogeneous mice at three sites.
Bottom line: strong geroscience rationale and mouse evidence do not establish longer human life.
Research record
What the evidence record says
- Evidence grade
- Limited human evidence
- Regulatory status
- FDA-approved for kidney-transplant rejection prophylaxis and lymphangioleiomyomatosis, but not for aging, longevity, or lifespan extension.
- Also known as
- sirolimus, Rapamune
Evidence records
Studies, registries, reviews, and regulatory records
PEARL
- Design: randomized, double-blind, placebo-controlled, decentralized, 48 weeks.
- Registry enrollment: 129 actual; paper reports 114 completers plus 11 withdrawals. The discrepancy should be left visible rather than harmonized without explanation.
- Intervention: compounded rapamycin labeled 5 mg or 10 mg weekly versus placebo.
- Primary result: no significant change in visceral adiposity at 48 weeks.
- Secondary signals: increased lean tissue mass and improved self-reported pain in women in the nominal 10 mg arm; some self-reported general-health measures in the nominal 5 mg arm.
- Safety: overall adverse-event counts were similar; gastrointestinal events were more frequent in rapamycin arms.
- Limits: the primary endpoint was null, enrollment and completion counts differ across records, and subgroup findings were exploratory.
- Exposure limit: the compounded study product produced about one-third the measured 24-hour blood concentration of commercial sirolimus.
- Conflict disclosure: the study was sponsored by AgelessRx and included authors with company relationships.
- Verdict: preliminary safety and healthspan-proxy evidence, not proof of slower aging or longer life.
Records: Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study (PEARL)., Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.
RAPA-EX-01
- Design: 40 sedentary adults aged 65–85, randomized double-blind trial, weekly sirolimus versus placebo during a 13-week home exercise program.
- Primary result: no enhancement of chair-stand performance in the intention-to-treat analysis.
- Sensitivity result: complete-case and per-protocol analyses suggested modest attenuation of training gains.
- Safety: higher burden of minor adverse events; one pneumonia hospitalization after one dose, with causality not excluded. Small LDL cholesterol and HbA1c increases were reported.
- Limitations: exploratory sample, 13 weeks, home-based training, no pharmacokinetic monitoring or muscle biopsy.
- Verdict: does not support claims that weekly rapamycin boosts exercise adaptation.
Preclinical evidence
- Harrison et al. began rapamycin at 600 days of age in genetically heterogeneous mice across three sites. At 90% mortality, lifespan increased 14% in females and 9% in males. The study could not determine whether this reflected delayed cancer, slower aging, or both.
Records: Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
Evidence timeline
What changed, and when
FDA approved Rapamune oral solution for prophylaxis of organ rejection after renal transplantation.
Nature published the three-site mouse study reporting late-life lifespan extension.
Records: Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
FDA approved sirolimus for lymphangioleiomyomatosis.
A 25-person placebo-controlled pilot examined feasibility and short-term safety in older adults.
PEARL results were published after 48 weeks of intermittent compounded rapamycin.
Records: Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.
RAPA-EX-01 reported no exercise benefit and possible attenuation in sensitivity analyses.
Direct answers
Frequently asked questions
Is rapamycin the same as sirolimus?
Yes. Sirolimus is the generic drug name; rapamycin is the widely used scientific name, and Rapamune is a brand name.
Records: Rapamune (sirolimus) oral solution and tablets, Prescribing Information.
Is rapamycin a peptide?
No. It is a macrolide compound and mTOR inhibitor.
Records: Rapamune (sirolimus) oral solution and tablets, Prescribing Information.
Has rapamycin extended lifespan in people?
No human trial has demonstrated lifespan extension. The best-known longevity result is from mice.
Records: Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results., Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
What did PEARL actually find?
It found no significant effect on its primary endpoint, visceral adiposity. Secondary subgroup signals included lean-tissue and pain changes in a small number of women.
Records: Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.
Why does the compounded formulation matter?
The study product produced about one-third the measured 24-hour blood concentration of commercial sirolimus, making nominal-dose comparisons difficult.
Records: Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.
Does rapamycin interfere with exercise adaptation?
A 2026 exploratory trial found no benefit and possible modest attenuation in sensitivity analyses, but larger and longer studies are needed.
Open research questions
What is still unknown
- Does any regimen improve human survival or disability-free survival?
- Can a schedule selectively affect mTORC1 without unacceptable immune or metabolic effects?
- Are PEARL's sex-specific secondary signals reproducible?
- How does intermittent rapamycin interact with resistance training over longer periods?
- What are multi-year infection, cancer, glucose, lipid, wound-healing, and reproductive risks in healthy adults?
- Which biomarkers, if any, predict human geroprotective benefit?
Tracked claims
Rapamycin extends human lifespan.
Evidence level: Unsupported by the cited record
Sources: Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results., Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
How to read this: Lifespan extension is established in mice, not humans.
Rapamycin is FDA-approved for anti-aging.
Evidence level: Contradicted by the cited record
Sources: Rapamune (sirolimus) oral solution and tablets, Prescribing Information., Sirolimus/Rapamune for lymphangioleiomyomatosis.
How to read this: FDA indications are kidney-transplant rejection prophylaxis and LAM.
Weekly low-dose rapamycin is proven safe for long-term use by healthy adults.
Evidence level: Overstated
Sources: Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.
How to read this: PEARL supplies 48-week exploratory data with formulation, subgroup, and analysis limitations.
Rapamycin builds muscle or improves workouts.
Evidence level: Mixed evidence
Sources: Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results., Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA-EX-01 Randomised, Double-Blind, Placebo-Controlled Trial.
How to read this: PEARL reported a small female subgroup signal, while RAPA-EX-01 found no benefit and possible attenuation of exercise gains.
Rapamycin prevents cancer in healthy people.
Evidence level: Unsupported by the cited record
Sources: Rapamune (sirolimus) oral solution and tablets, Prescribing Information., Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
How to read this: Mouse survival effects may partly involve delayed cancer, while the drug label warns that immunosuppression can increase lymphoma and other malignancy risk.
PEARL proved anti-aging efficacy.
Evidence level: Contradicted by the cited record
Sources: Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.
How to read this: The primary endpoint was null and the trial did not measure lifespan or a validated aging-rate endpoint.
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Sources on this page
Each source record is linked to the claim or evidence note it supports.
Rapamune (sirolimus) tablets: Medical Review.
FDA Center for Drug Evaluation and Research. Rapamune (sirolimus) tablets: Medical Review. NDA 21-110. 2000. Notes prior oral-solution approval on 1999-09-15.
research-rapa-01Rapamune (sirolimus) oral solution and tablets, Prescribing Information.
U.S. Food and Drug Administration. Rapamune (sirolimus) oral solution and tablets, Prescribing Information. Revised August 2022. Reference ID 5033875.
research-rapa-02Sirolimus/Rapamune for lymphangioleiomyomatosis.
U.S. Food and Drug Administration, Orphan Drug Designations and Approvals. Sirolimus/Rapamune for lymphangioleiomyomatosis. Marketing approval 2015-05-28.
research-rapa-03Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study (PEARL).
ClinicalTrials.gov. Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study (PEARL). NCT04488601. Sponsor: AgelessRx. Last update posted 2024-01-24.
research-rapa-04Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.
Moel M, Harinath G, Lee V, et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging (Albany NY). 2025;17(4):908-936. doi:10.18632/aging.206235. PMID 40188830; PMCID PMC12074816.
research-rapa-05Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA-EX-01 Randomised, Double-Blind, Placebo-Controlled Trial.
Stanfield B, Leroux B, Kaeberlein M, Jones J, Lucas R. Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA-EX-01 Randomised, Double-Blind, Placebo-Controlled Trial. J Cachexia Sarcopenia Muscle. 2026;17(2):e70274. doi:10.1002/jcsm.70274. PMID 41985884; PMCID PMC13082878.
research-rapa-06Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392-395. doi:10.1038/nature08221. PMID 19587680; PMCID PMC2786175.
research-rapa-07A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: immunological, physical performance, and cognitive effects.
Kraig E, Linehan LA, Liang H, et al. A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: immunological, physical performance, and cognitive effects. Exp Gerontol. 2018;105:53-69. PMID 29408453.
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