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Rapamycin

Rapamycin (sirolimus) is a prescription-only immunosuppressant medicine that some people take off-label in the hope of slowing ageing. In genetically heterogeneous mice in the NIA Interventions Testing Program it extended lifespan, even when started late in life. In people, the trials are small and short and measure surrogate outcomes: a low-dose mTOR-inhibitor trial improved influenza vaccine response in older adults, and the 48-week PEARL trial in healthy adults found no change in its primary outcome. No trial has shown that rapamycin extends human lifespan or healthspan. Documented adverse effects include mouth sores, rash, gastrointestinal upset, lower red blood cell measures, more infections and raised blood lipids, and the medicine's label warns of serious infection and cancer risk. No claim reaches moderate or high certainty because the human evidence consists of a few small, short trials on surrogate outcomes and the lifespan evidence comes from mice.

  • Longevity

Evidence retrieved up to

What the research shows

In genetically heterogeneous laboratory mice in the NIA Interventions Testing Program, rapamycin added to food extended median and maximal lifespan in both males and females, including when started late in life, with the effect seen at three independent test sites.

Low certaintyFurther research is likely to change this.
Take care: see the safety noteBenefit

Who this is about

genetically heterogeneous laboratory mice (UM-HET3)

Practical note

Graded low for what it implies about people: the mouse finding is consistent and was replicated across three sites and later ITP cohorts, but it is downgraded for indirectness, because lifespan in mice does not establish any effect on human lifespan.

Safety note

This is animal evidence and says nothing directly about safety or benefit in people. Rapamycin is a prescription-only immunosuppressant medicine.

Sources

In a placebo-controlled trial in older adults, a low-dose course of the rapamycin derivative everolimus (RAD001) was followed by an influenza vaccine response about 20% higher than placebo, an immune-function surrogate rather than a health outcome.

Low certaintyFurther research is likely to change this.
Take care: see the safety noteBenefit

Who this is about

older adults

Practical note

Graded low: one industry-run randomised trial with a surrogate outcome (vaccine antibody response), downgraded for indirectness and imprecision. A 2024 systematic review of 19 human studies reported improvements in immune parameters but found no significant effects on endocrine, muscular or neurological systems.

Safety note

Everolimus and rapamycin are prescription-only immunosuppressant medicines. The trial reported the doses as relatively well tolerated over a short course.

Sources

In the 48-week PEARL trial of intermittent low-dose rapamycin in healthy adults, the primary outcome, visceral fat, did not change compared with placebo; a few secondary measures (lean tissue mass and pain in women on the higher dose, self-rated well-being on the lower dose) improved, and adverse events were similar across groups.

Low certaintyFurther research is likely to change this.
Take care: see the safety noteNo clear effect

Who this is about

healthy adults with normal ageing

Practical note

Graded low: a single randomised trial whose primary outcome was null; the positive findings are secondary and subgroup results open to multiple-comparison error, and the authors are employees and shareholders of AgelessRx, a commercial company (risk of bias). The trial used compounded rapamycin once a week.

Safety note

Adverse events were similar to placebo over 48 weeks in this healthy cohort, but the trial was not large or long enough to detect rarer or later harms. Rapamycin is a prescription-only medicine.

Sources

No trial has shown that rapamycin or its derivatives extend human lifespan or healthspan; the human studies so far are small and short, measure surrogate markers, and their authors call for larger and longer trials.

Very low certaintyThis is uncertain; treat it as a lead, not a finding.
Take care: see the safety noteUnclear

Who this is about

adults

Practical note

Graded very-low for any effect on human ageing outcomes: there are no trials with lifespan or validated healthspan endpoints, and the available trials are small, short and use surrogate outcomes (serious indirectness and imprecision).

Safety note

Rapamycin is a prescription-only immunosuppressant medicine; its use for ageing is off-label.

Sources

Documented adverse effects of rapamycin and its derivatives at the doses studied include mouth sores, rash, gastrointestinal upset and lower red blood cell measures in healthy older adults, and more infections and higher total cholesterol, LDL cholesterol and triglycerides in adults with ageing-related diseases; as a licensed immunosuppressant medicine it carries warnings of serious infection and of cancer, especially lymphoma and skin cancer.

Low certaintyFurther research is likely to change this.
Caution: see the safety noteRisk

Who this is about

adults taking rapamycin or its derivatives

Practical note

Graded low: the adverse-event data come from small, short trials and a 2024 systematic review of 19 studies; harms at transplant doses are documented in the medicine's labelling, but how they scale to the lower or intermittent doses used in ageing trials is uncertain (indirectness, imprecision). The pilot trial in older adults gave a small daily dose for at least 8 weeks.

Safety note

Rapamycin (sirolimus) is a prescription-only medicine that suppresses the immune system. It interacts with other medicines and needs medical supervision; any use belongs with the prescribing clinician.

Sources