§ 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
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
4 articles from the last 12 months · updates hourly
Which Drugs Interact With Paxlovid? - Verywell Health
Which Drugs Interact With Paxlovid? Verywell Health
Science & Medicine: A pill that slows aging? San Antonio researchers are putting it to the test - Texas Public Radio | TPR
Science & Medicine: A pill that slows aging? San Antonio researchers are putting it to the test Texas Public Radio | TPR
A billion-dollar drug was found in Easter Island soil – what scientists and companies owe the Indigenous people they studied - The Conversation
A billion-dollar drug was found in Easter Island soil – what scientists and companies owe the Indigenous people they studied The Conversation
Rapamycin’s Effects on Human Aging Explored in New Study - Newsweek
Rapamycin’s Effects on Human Aging Explored in New Study Newsweek
§ 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.
Telehealth (Rx) · 2
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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 Questions
Rapamycin (Sirolimus) FAQ
- What is Rapamycin (Sirolimus)?
- 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. 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.
- What is Rapamycin (Sirolimus) used for?
- Reported uses include extends mouse lifespan (harrison 2009 and later), improves physical and cognitive markers (pearl trial), and potential senomorphic + autophagy-inducing effects. Evidence strength is rated Established — see the evidence section for detail.
- How is Rapamycin (Sirolimus) dosed?
- Commonly referenced dosing is 6 mg weekly (off-label longevity protocols), administered Oral. This is educational reference only; consult a licensed clinician before use.
- What are the side effects of Rapamycin (Sirolimus)?
- Commonly reported side effects include mouth ulcers, immunosuppression at higher / daily dosing, and dyslipidemia and glucose elevations. This list is not exhaustive.
- Is Rapamycin (Sirolimus) legal?
- 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. FDA status: FDA-approved (Rapamune NDA 021083) for transplant rejection and LAM..
§ 11 References
Selected references
- 01
Harrison Nature — mouse lifespan
PMID: 19587680
- 02
PEARL trial
PMID: 40188830 (NCT04488601)