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Research · Medication

Rapamycin

Human aging trials of rapamycin are small and short. In the 48-week PEARL trial, weekly low-dose rapamycin did not change visceral fat, its main outcome. In older adults doing home exercise, weekly sirolimus did not add to gains, and placebo did better in sensitivity analyses. No human lifespan trial was sourced. Transplant data show infection, lipid and mortality signals.

Add to Bio HackChecked 2026-11-09
Status
Prescription drug in the US. Sirolimus is FDA-approved to prevent organ rejection in kidney transplant recipients aged 13 and older and to treat lymphangioleiomyomatosis (LAM). It carries a boxed warning on immunosuppression. It is not approved for aging or longevity, and that use is off-label.
Also called
sirolimus, Rapamune, rapa, mTOR inhibitor, rapalog, everolimus
Taken for
longevity, anti-aging, healthspan, lifespan, immune aging, muscle in older age

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help2

Reported risks4

What people take it for, and what was found

Shown to help2

Limited

Immune response to vaccines and infections in older adults

Small trials of rapamycin analogs, not sirolimus, found a better flu vaccine response and fewer reported infections in older adults.

The numbers and sources
Effect
The rapamycin analog everolimus (RAD001) raised the response to influenza vaccine by about 20% in older volunteers [4]. A low-dose combination of everolimus and BEZ235 taken for 6 weeks was associated with fewer reported infections over the following year (P = 0.001) and a better influenza vaccine response [5].
Population
Older volunteers [4]; 264 older adults in a phase 2a trial [5].
Sources
[4], [5]
Caveats
These trials tested rapamycin analogs, not sirolimus itself. Infections were self-reported [5]. [5] lists Novartis funding.
Strong

Cancer in kidney transplant recipients

Shown to lower cancer and skin cancer in kidney transplant recipients against other regimens, with new skin squamous cell cancers about halved.

The numbers and sources
Effect
Against regimens without it, sirolimus was associated with a lower risk of cancer (adjusted HR 0.60, 95% CI 0.39 to 0.93) and of non-melanoma skin cancer (HR 0.44, 95% CI 0.30 to 0.63). The reduction was largest in people switched to sirolimus from an established regimen [6]. In recipients who had already had a cutaneous squamous cell carcinoma, switching from a calcineurin inhibitor to sirolimus lowered 2-year incidence of a new one (IRR 0.51, 95% CI 0.39 to 0.67), with certainty rated high [7].
Population
Individual data from 5,876 kidney or kidney-pancreas transplant recipients in 21 RCTs [6]; 4 RCTs with 393 kidney transplant recipients with prior skin squamous cell carcinoma [7].
Sources
[6], [7]
Caveats
The same analysis found higher mortality on sirolimus (see Risks) [6]. Stopping for adverse events was more common on sirolimus in [7]. It describes transplant recipients on combined immunosuppression, not healthy adults.

Not shown to help2

Limited

Healthspan measures in healthy older adults

Small trials found no change in visceral fat, cognition or physical performance in healthy older adults, with only scattered gains in subgroups.

The numbers and sources
Effect
Over 48 weeks, weekly rapamycin 5 mg or 10 mg did not change visceral fat on DXA, the primary outcome, against placebo (p = 0.942). Blood biomarkers stayed in normal ranges. Lean tissue mass and self-reported pain improved in women on 10 mg, and emotional well-being and general health scores improved on 5 mg. No other effects were significant [1]. In a pilot in adults aged 70 to 95, 8 weeks or more of rapamycin 1 mg daily did not change cognitive, physical performance or self-rated health measures, or glucose tolerance [2].
Population
Healthy adults in a decentralized 48-week trial [1]; 25 adults with mean age 80.5 [2].
Sources
[1], [2]
Caveats
The positive findings in [1] were in subgroups among many secondary outcomes. [1] used compounded rapamycin. Both trials were small.
Limited

Physical function with exercise in older adults

Small trials found no gain in physical function with exercise, and one found smaller chair-stand gains on sirolimus than placebo in some analyses.

The numbers and sources
Effect
Over 13 weeks of home exercise, chair-stand repetitions rose in both groups. The difference was -2.13 repetitions (95% CI -4.61 to 0.34) for sirolimus 6 mg weekly against placebo. Complete-case (-2.46) and per-protocol (-3.44) analyses favored placebo significantly. Six-minute walk and grip strength also favored placebo, not significantly [3]. Handgrip and timed walk did not change on rapamycin 1 mg daily in the pilot [2].
Population
40 sedentary adults aged 65 to 85, mean 72.2 [3]; 25 adults aged 70 to 95 [2].
Sources
[3], [2]
Caveats
Small exploratory trials. [3] was funded by Dr Brad Stanfield Ltd.

Claimed, not studied in people1

Untested

Longer human lifespan

Not studied in people. Started late in life, rapamycin lengthened median and maximum lifespan in both male and female mice at three test sites.

No study in people. This rests on animal studies.

The numbers and sources
Effect
In genetically mixed mice fed rapamycin from 600 days of age, median and maximum lifespan rose in both sexes. Age at 90% mortality rose 14% in females and 9% in males, at three independent sites, and disease patterns did not differ from controls. Mice started at 270 days of age also survived longer at an interim analysis [9]. No study measuring lifespan in people taking rapamycin was located. In kidney transplant recipients, mortality was higher on sirolimus (see Risks) [6].
Population
Genetically heterogeneous mice at three sites [9].
Sources
[9], [6]
Caveats
Mouse lifespan does not show what happens in people. The transplant finding comes from people on combined immunosuppression, not healthy adults, and does not measure aging [6].

Doses studied

PEARL used compounded rapamycin 5 mg or 10 mg once weekly for 48 weeks [1]. The exercise trial used sirolimus 6 mg once weekly for 13 weeks [3]. The pilot in older adults used rapamycin 1 mg daily [2].

Risks

Reported risks4

ModerateVery common

High cholesterol and triglycerides

Shown to raise high cholesterol and triglycerides in kidney transplant recipients, 43 to 57% against 23% on placebo. Low weekly doses kept markers in range.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In the label's kidney transplant trials, high cholesterol occurred in 43% to 46% and high triglycerides in 45% to 57% on sirolimus, against 23% for each on placebo. Up to 90% of people on sirolimus with cyclosporine needed treatment for high lipids [8].
Population
Kidney transplant recipients in the label's controlled studies [8].
Sources
[8]
Caveats
In PEARL, blood biomarkers stayed in normal ranges at weekly low doses [1].
LimitedVery common

Mouth sores, gut effects and blood count changes

Small trials found mouth sores, rash and gut problems in a few older adults, and falls in red cell counts without clinical effects.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In the pilot, adverse effects on rapamycin were a facial rash (1), mouth sores (1) and gastrointestinal problems (2), against mouth sores (1) on placebo. Hemoglobin, hematocrit and red cell count fell on rapamycin, without clinical effects over the study [2]. In LAM, the label lists mouth sores, diarrhea, abdominal pain, nausea, acne and swelling among reactions in 20% or more [8].
Population
25 older adults [2]; LAM patients in the label [8].
Sources
[2], [8]
Caveats
Small numbers. In PEARL, adverse events did not differ across groups [1].
ModerateHow often is not known

Higher mortality in kidney transplant recipients

Shown to raise death about 43% in kidney transplant recipients against other regimens, at transplant doses with other immunosuppressants.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Sirolimus was associated with an increased risk of death against control regimens (HR 1.43, 95% CI 1.21 to 1.71) [6]. In 4 RCTs of recipients with prior skin squamous cell carcinoma, mortality and graft rejection did not differ, while stopping because of adverse events was more common on sirolimus (RR 8.60, 95% CI 1.95 to 37.93) [7].
Population
5,876 kidney transplant recipients in 21 RCTs [6]; 393 recipients in 4 RCTs [7].
Sources
[6], [7]
Caveats
Recipients took sirolimus alongside other immunosuppressants, at transplant doses. [7] rated certainty for adverse events low.
LimitedHow often is not known

Infection and lymphoma (boxed warning)

The label warns immunosuppression may increase infection and the possible development of lymphoma and other malignancies, at transplant doses.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label's boxed warning states that immunosuppression may increase susceptibility to infection and the possible development of lymphoma and other malignancies. It reports excess mortality, graft loss and hepatic artery thrombosis in liver transplant and bronchial anastomotic dehiscence in lung transplant. The label lists latent viral infections, interstitial lung disease and impaired wound healing among its warnings [8]. In the exercise trial, 85% in each arm reported an adverse event, with 99 events on sirolimus against 63 on placebo, and one possibly drug-related pneumonia [3].
Population
Transplant recipients, summarized in the label [8]; 40 older adults [3].
Sources
[8], [3]
Caveats
The label describes transplant doses with other immunosuppressants. Aging trials were too small to measure rare serious infections.

Sources

  1. Moel M, Harinath G, Lee V, et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging. 2025. https://doi.org/10.18632/aging.206235
  2. 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. Experimental Gerontology. 2018. https://doi.org/10.1016/j.exger.2017.12.026
  3. Stanfield B, Leroux B, Kaeberlein M, et al. Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA-EX-01 Randomised, Double-Blind, Placebo-Controlled Trial. Journal of Cachexia, Sarcopenia and Muscle. 2026. https://doi.org/10.1002/jcsm.70274
  4. Mannick JB, Del Giudice G, Lattanzi M, et al. mTOR inhibition improves immune function in the elderly. Science Translational Medicine. 2014. https://doi.org/10.1126/scitranslmed.3009892
  5. Mannick JB, Morris M, Hockey HUP, et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Science Translational Medicine. 2018. https://doi.org/10.1126/scitranslmed.aaq1564
  6. Knoll GA, Kokolo MB, Mallick R, et al. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data. BMJ. 2014. https://doi.org/10.1136/bmj.g6679
  7. Foerster Y, Palaras J, Mayer K, et al. Sirolimus for Secondary Prevention of Cutaneous Squamous Cell Carcinoma in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. International Journal of Dermatology. 2026. https://doi.org/10.1111/ijd.70285
  8. U.S. Food and Drug Administration. Sirolimus tablets, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57fb4d90-3ccb-4a69-af1e-53be83f7a504
  9. Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009. https://doi.org/10.1038/nature08221

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