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EstablishedLongevityOralWeekly

Rapamycin (Sirolimus)

Rapamune

Macrolide mTORC1 inhibitor, FDA-approved for transplant rejection and LAM; weekly off-label dosing extends lifespan in mice and showed benefits in the PEARL human trial.

◆ Editorial note

Macrolide small molecule. FKBP12/mTORC1 inhibitor.

§ 01   Overview

Overview

Macrolide mTORC1 inhibitor, FDA-approved for transplant rejection and LAM; weekly off-label dosing extends lifespan in mice and showed benefits in the PEARL human trial.

FDA-approved for transplant rejection (1999) and LAM (2015). PEARL RCT (2025) is the first human longevity-endpoint trial.

§ 02   Mechanism

Mechanism of action

Rapamycin forms a complex with FKBP12 that inhibits mTORC1, dampening cell growth and protein synthesis pathways and activating autophagy. Intermittent dosing preserves mTORC1 recovery and appears to avoid mTORC2-related metabolic side effects.

  • 01Extends mouse lifespan (Harrison 2009 and later)
  • 02Improves physical and cognitive markers (PEARL trial)
  • 03Potential senomorphic + autophagy-inducing effects

§ 03   Dosing

Dosing protocol

Standard Protocol

Dose Range
6 mg weekly (off-label longevity protocols)
Route
Oral
Timing
Same day weekly
Frequency
Weekly
Cycle
Continuous; reassess IGF-1, lipids, glucose

§ 04   Evidence

Evidence & research

Established

FDA-approved for transplant rejection (1999) and LAM (2015). PEARL RCT (2025) is the first human longevity-endpoint trial.

FDA Status

FDA-approved (Rapamune NDA 021083) for transplant rejection and LAM.

§ 06   News

In the news

8 articles from the last 12 months · updates hourly

Business WireJul 30, 2025

Felycin®-CA1 (Sirolimus Delayed-Release Tablets) is the First and Only Drug FDA Approved for the Management of Ventricular Hypertrophy in Cats with Subclinical Hypertrophic Cardiomyopathy (HCM), A Condition Affecting as Many as One in Seven Cats - Business Wire

Felycin®-CA1 (Sirolimus Delayed-Release Tablets) is the First and Only Drug FDA Approved for the Management of Ventricular Hypertrophy in Cats with Subclinical Hypertrophic Cardiomyopathy (HCM), A Condition Affecting as Many as One in Seven Cats Business Wire

§ 07   Sourcing

Sourcing & supply

Regulatory status

FDA-approved

This compound has an FDA approval for at least one indication. Brand pharmacy channels exist. Compounding may or may not be available depending on shortage status.

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§ 09   Safety

Safety & side effects

Side effects

  • 01Mouth ulcers
  • 02Immunosuppression at higher / daily dosing
  • 03Dyslipidemia and glucose elevations

Contraindications

  • 01Active infection
  • 02Pregnancy

§ 10   References

Selected references

  1. 01

    Harrison Nature — mouse lifespan

    PMID: 19587680

  2. 02

    PEARL trial

    PMID: 40188830 (NCT04488601)

This site is for educational and research purposes only. It does not constitute medical advice. Always consult a qualified healthcare provider before using any peptide or supplement.