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Rapamycin (Sirolimus)

Aliases: Sirolimus · Rapamune

Last verified: 2026-09-23

Approved drugStrong evidenceSmall moleculesHigh interest

The short version

Rapamycin (sirolimus) is one of the most significant molecules in the biology of aging: it extends lifespan in nearly every model organism (in mice even when given late in life), and in humans it is an approved immunosuppressant with decades of use. The TENS trial showed that intermittent low dosing can improve immune response in older adults — the first major positive human signal. But: it is also an immunosuppressant with real risks (infections, delayed wound healing, lipid effects). 'Longevity dosing' is an active research field, not a finished answer.

Identity & type

Molecular type
small-molecule
Sequence / structure
— (makrolidni imunosupresant)
Molecular weight
~914 Da
Formula
C51H79NO13
Origin
Macrolide from Streptomyces hygroscopicus, discovered on Rapa Nui island; mTOR pathway inhibitor.

Mechanism of action

Inhibits mTORC1 → autophagy, reduced cellular senescence, immunomodulation.

Dosing & routes

Official / clinical context

Approved drug — indications, dosing and warnings are defined by the official label. Longevity protocols: 3–10 mg once weekly; transplant: daily per TDM.

Regulator-approved labeling and published study designs — never a recommendation.

Community-reported practice

Longevity protocols: 3–10 mg once weekly; transplant: daily per TDM. The longevity community (weekly dosing): reduced "inflammaging" symptoms and better blood work in some; in others mouth ulcers and slower scratch healing. Highly individual.

Unverified self-reports. Not medical advice. Not endorsement.

Expected effects (community)

The longevity community (weekly dosing): reduced "inflammaging" symptoms and better blood work in some; in others mouth ulcers and slower scratch healing. Highly individual.

Protocol — official vs community

Official / label

Approved (sirolimus): transplant/antiproliferative dosing 1–10 mg/day depending on indication and trough targets. Longevity-oriented physicians typically use 5–10 mg once WEEKLY with an sirolimus trough check.

  1. 01Start 2–5 mg weekly
  2. 02Titrate by trough level, side effects (lipids, glucose, mouth ulcers)

Duration: Continuous under supervision for approved use; longevity use is indefinite, physician-monitored.

mTOR inhibition is the mechanism; the weekly pulse schedule is a longevity-clinic convention aimed at side-effect reduction.

Community (anecdotal)

5–10 mg oral once weekly, often with a high-fat meal for absorption; some add grapefruit juice to slow metabolism (increases exposure — a real pharmacokinetic interaction).

Cycle:
Continuous weekly, or 6 weeks on / 2 off in some protocols.
Break:
Periodic labs: lipids, glucose, CBC; hold for surgery, infection, mouth ulcers.

The best-evidence longevity drug in the codex — and the one where DIY use most forfeits the monitoring that makes it defensible.

Human evidence

Approved for transplantation and LAM; TENS phase II (Mannick, 2014) showed improved immune response; open-label longevity trials (PEP-EarlyAd) are ongoing.

Preclinical evidence

The preclinical phase was completed and submitted to regulators as part of registration; pharmacology and toxicology details are part of the official label.

Known risks

  • Infections, mucositis, delayed wound healingcharacterized
  • Dyslipidemia, hyperglycemia (mTOR blockade in metabolic tissues)characterized
  • Theoretical immunodeficiency risk with chronic low dosetheoretical

Teal: characterized in clinical/labeling contexts. Amber: theoretical or reported outside controlled settings.

Unknowns & evidence gaps

  • Optimal regimen for 'longevity' (intermittent vs continuous)
  • Effect on actual human lifespan

Frequently asked questions

References

  1. Harrison D.E. et al., rapamycin extends mouse lifespan (Nature, 2009)
  2. Mannick J.B. et al., TENS phase II (Sci Transl Med, 2014)
  3. Kaeberlein M. et al., rapamycin in the biology of aging (review)