The TL;DR
Rapamycin is currently the most promising longevity drug on the planet. Originally discovered in soil bacteria on Easter Island (Rapa Nui), it is an FDA-approved immunosuppressant for transplant patients. However, at low, intermittent doses, it inhibits mTOR, mimicking the effects of fasting and caloric restriction. It has extended lifespan in every model organism tested, including mice (by up to 26%).
Accessibility Level
Level 4 (Experimental): It is a prescription drug. Using it for longevity is “off-label” and requires a willing physician. It is not without risks.
The Science of Rapa
Rapamycin works by binding to mTORC1 (mechanistic Target of Rapamycin Complex 1).
- mTORC1 is the “growth switch.” When it’s on, cells grow. When it’s off, cells repair (autophagy).
- The Problem: In modern life (constant food), mTOR is stuck “On.”
- The Fix: Rapamycin turns it “Off,” triggering deep cellular cleaning and rejuvenation.
The “Side Effects” Myth
High daily doses (transplant protocol) suppress the immune system and cause diabetes. Low weekly doses (Longevity protocol) appear to boost immune function (e.g., better vaccine response in the elderly) and have a much milder side effect profile (mouth sores are the most common).
Evidence Matrix
| Source | Verdict | Notes |
|---|---|---|
| NIA ITP Study | Gold Standard | The Interventions Testing Program (ITP) proved it extends lifespan in genetically diverse mice (late-life administration). |
| Dog Aging Project | Ongoing | Currently testing Rapamycin in pet dogs (TRIAD trial) to see if it extends life in a large mammal living in the human environment. |
| PEARL Trial | Ongoing | Human trial testing safety and efficacy of weekly Rapamycin. |
| Dr. Alan Green | Practitioner | Has treated 1000+ patients with off-label Rapamycin; reports low adverse events. |
The Protocol (Hypothetical)
Disclaimer: This is not medical advice. This reflects common protocols in the longevity community.
- Dosing: Weekly (not daily). This allows mTOR to rebound, preventing immune suppression while triggering autophagy.
- Typical Range: 2mg to 6mg once per week.
- Timing: Often taken in the morning (can be stimulating).
- Cycling: Some users take “holidays” (e.g., 8 weeks on, 2 weeks off) to prevent adaptation.
Risks & Considerations
- Lipids: Often raises lipids (cholesterol/triglycerides). Users may need to pair it with lipid-lowering therapy.
- Glucose: Can cause “benevolent” insulin resistance (glucose sparing), or actual insulin resistance. Monitoring is key.
- Infection: Theoretical risk of bacterial infections due to immune modulation.
- Fertility: Can reversibly reduce sperm count/quality.
References
Harrison, D. E., et al. (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature.
Mannick, J. B., et al. (2014). mTOR inhibition improves immune function in the elderly. Science Translational Medicine.
Blagosklonny, M. V. (2019). Rapamycin for longevity: opinion article. Aging.