Key Takeaways
- Rapamycin (sirolimus) is the most robust lifespan-extending drug in animal studies — extending mouse lifespan by 9–26% even when started late in life.
- For longevity, it's used at low, intermittent doses (3–8mg once weekly or biweekly) — vastly different from daily immunosuppressive doses in transplant patients.
- Key protocols: Kaeberlein's 5–6mg weekly, Attia's cycling approach (6–8 weeks on, 4–8 weeks off).
- Essential blood work monitoring: lipids (will rise), glucose/HbA1c (may rise), CBC, liver panel.
- In Malaysia, rapamycin is available by prescription (brand: Rapamune). Cost: RM 30–80 per 1mg tablet.
Medical disclaimer: Rapamycin is a prescription immunosuppressant. This article is for education only. Do NOT self-medicate. Work with a knowledgeable physician.
Why Rapamycin Is the Longevity Community's Favourite Drug
No drug in history has a more consistent lifespan-extending track record than rapamycin. Originally discovered in soil bacteria from Easter Island (Rapa Nui — hence the name), rapamycin inhibits mTOR (mechanistic Target of Rapamycin), a master growth-regulating pathway.
The evidence is extraordinary:
- Every organism tested — from yeast to worms to flies to mice — shows lifespan extension with rapamycin or mTOR inhibition
- The NIA Interventions Testing Program showed rapamycin extended mouse lifespan by 9–14% in males and 13–26% in females
- Even when started at 20 months old (equivalent to ~60 human years), rapamycin still extended lifespan
- Matt Kaeberlein's Dog Aging Project showed improved cardiac function in pet dogs after just 10 weeks
For a broader overview of rapamycin in longevity, see our rapamycin longevity guide. This article focuses on dosing protocols and practical implementation.
How Rapamycin Works: mTOR Inhibition
mTOR is a nutrient-sensing pathway that acts as a growth/repair switch:
- mTOR active (high nutrients, growth signals): Cell growth, protein synthesis, proliferation. Good for building muscle. Bad when chronically overactivated — drives aging, cancer, and metabolic dysfunction.
- mTOR inhibited (fasting, rapamycin): Autophagy (cellular cleanup), stress resistance, DNA repair. The "maintenance and repair" mode associated with longevity.
mTORC1 vs mTORC2: The Selectivity Problem
mTOR exists in two complexes:
- mTORC1 — inhibition is beneficial (reduces inflammation, activates autophagy, extends lifespan)
- mTORC2 — inhibition causes side effects (insulin resistance, lipid dysregulation, immune suppression)
Short-acting, intermittent rapamycin dosing preferentially inhibits mTORC1 while allowing mTORC2 to recover between doses. This is the theoretical basis for weekly dosing over daily dosing.
Dosing Protocols: What the Experts Use
Matt Kaeberlein's Protocol
- Dose: 5–6mg once weekly
- Cycling: Continuous weekly dosing (no cycling off)
- Monitoring: Regular blood work — lipids, glucose, HbA1c, CBC
- Rationale: Based on Dog Aging Project scaling (0.1mg/kg 3×/week in dogs ≈ 5–6mg weekly in humans)
Peter Attia's Approach
- Dose: 5–8mg once weekly (varies by patient)
- Cycling: 6–8 weeks on, 4–8 weeks off
- Grapefruit juice: Sometimes used to boost bioavailability (inhibits CYP3A4), allowing a lower pill dose
- Blood work: Comprehensive monitoring before, during, and after each cycle
Alan Green, MD — The Rapamycin Clinician
Dr. Alan Green, a New York physician, has prescribed rapamycin for longevity to 1,500+ patients:
- Dose: 3–6mg once weekly
- Continuous: No cycling
- Starting low: Often begins at 3mg weekly, titrates up based on response
Protocol Comparison
| Protocol | Dose | Frequency | Cycling | Key Feature |
|---|---|---|---|---|
| Kaeberlein | 5–6mg | Weekly | Continuous | Dog Aging Project scaling |
| Attia | 5–8mg | Weekly | 6–8 wks on, 4–8 off | Cautious, individualized |
| Green | 3–6mg | Weekly | Continuous | Most clinical experience |
| Conservative start | 3mg | Biweekly | 3 months on, 1 off | For cautious first-timers |
Blood Work Monitoring: Non-Negotiable
Testing Schedule
| Timing | Tests |
|---|---|
| Baseline (before starting) | Full lipid panel, HbA1c, fasting glucose, fasting insulin, CBC, liver panel, kidney panel, hsCRP |
| 4 weeks after starting | Lipid panel, glucose, CBC |
| 3 months | Full panel (repeat baseline) |
| Every 3–6 months ongoing | Full panel |
See our longevity blood test guide for where to get these tests in Malaysia.
Expected Changes
| Marker | Expected Change | Action If Concerning |
|---|---|---|
| LDL / Total Cholesterol | ↑ 10–30% | If ApoB rises above 100 mg/dL, consider statin or dose reduction |
| Triglycerides | ↑ 10–20% possible | Omega-3 supplementation helps |
| Fasting Glucose | ↑ 5–15% possible | If HbA1c exceeds 5.7%, reduce dose or cycle off |
| HbA1c | May ↑ 0.1–0.3% | Key marker to watch |
| WBC / Platelets | Usually stable | If WBC drops below 3.5, stop and reassess |
| hsCRP | Often ↓ (good) | Rapamycin is anti-inflammatory |
The lipid paradox: Rapamycin raises LDL cholesterol in most people. Whether the anti-inflammatory and autophagy benefits outweigh the lipid increase in net cardiovascular risk remains debated. Many clinicians add a low-dose statin if lipids rise significantly.
Side Effect Management
Common (at Longevity Doses)
- Mouth sores (aphthous ulcers) — most common complaint. Usually mild. Management: lower dose, canker sore gel, good oral hygiene. Some use dexamethasone mouthwash.
- Mild GI upset — nausea, loose stools. Usually transient.
- Skin changes — occasional acne-like eruptions.
- Delayed wound healing — clinically relevant. Stop rapamycin 2–4 weeks before elective surgery.
Serious (Rare at Longevity Doses)
- Immune modulation — at transplant doses (daily), rapamycin profoundly suppresses immunity. At weekly longevity doses, evidence suggests immunity may actually be enhanced (Mannick et al., 2014, Science Translational Medicine — improved vaccine responses in elderly). Skip your dose if actively sick.
- Pneumonitis — rare inflammatory lung reaction. Persistent cough or breathlessness = stop immediately, see doctor.
- Significant metabolic derangement — if glucose or lipids rise substantially, risk may outweigh benefit.
Combining With Other Longevity Interventions
Rapamycin + Metformin
Both inhibit mTOR-related pathways through different mechanisms. Metformin may offset rapamycin's glucose-raising effect. However, ITP studies showed combining both in mice didn't extend lifespan beyond rapamycin alone.
Rapamycin + NMN/NR
Complementary: NAD+ supports repair while rapamycin promotes autophagy. No known negative interactions. Commonly combined.
Rapamycin + Fasting
Both activate autophagy. Some take their weekly dose on a fasting day to maximize mTOR inhibition. Mechanistically logical, though unproven in trials.
Rapamycin + Senolytics
Rapamycin may slow new senescent cell formation; senolytics clear existing zombie cells. The "prevention + cleanup" strategy.
What NOT to Combine
- Other immunosuppressants — additive immune suppression
- Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) — dramatically increase rapamycin levels, risking toxicity
- Live vaccines — avoid during active use
Accessing Rapamycin in Malaysia
The Prescription Path
Rapamycin (sirolimus) is available in Malaysia as Rapamune (Pfizer) and generic versions.
- Standard route: Prescription from a licensed medical practitioner. Primarily prescribed by nephrologists/transplant physicians.
- Off-label for longevity: Very few Malaysian doctors currently prescribe off-label. You may need to educate your doctor or find a functional medicine practitioner.
- Cost: RM 30–80 per 1mg tablet (branded). At 5mg weekly = RM 150–400/month. Generics may be cheaper.
What to Bring to Your Doctor
If you're requesting rapamycin from a Malaysian physician unfamiliar with longevity dosing:
- Published research — the Mannick et al. (2014) paper showing improved immune function with mTOR inhibition in elderly; the ITP data showing lifespan extension
- Your blood work — demonstrate you're health-literate and monitoring responsibly
- Clear protocol — "5mg once weekly, with quarterly blood monitoring" is easier for a doctor to accept than vague "anti-aging" requests
- Informed consent understanding — acknowledge it's off-label, understand the risks
Singapore as an Alternative
Several longevity clinics in Singapore prescribe rapamycin off-label. While more expensive, the doctors are familiar with longevity protocols and can provide proper supervision. Crossing the Causeway for a quarterly consultation may be worthwhile.
Who Should NOT Take Rapamycin
- Anyone with active infections or compromised immunity
- People planning surgery within 4 weeks
- Pregnant or breastfeeding women
- People with uncontrolled diabetes (rapamycin may worsen glucose control)
- Those with severe liver or kidney impairment
- Anyone not willing to do regular blood work monitoring
- People under 30 (insufficient risk-benefit at young ages)
A Practical Starting Framework
- Get comprehensive baseline blood work (full panel guide here)
- Find a willing physician — functional medicine, longevity-focused, or a sympathetic GP
- Start conservatively: 3mg biweekly for the first month
- Recheck blood work at 4 weeks
- If tolerated, increase to 5mg weekly
- Full panel at 3 months — assess lipids, glucose, HbA1c, CBC
- Adjust or continue based on data
- Track everything — maintain a spreadsheet of doses, blood work, side effects, subjective wellbeing
Bottom Line
Rapamycin is the most evidence-backed lifespan-extending drug in existence — in animals. Human longevity trials are underway but not yet conclusive. The longevity community has largely moved from "if" to "how" — and the protocols described here represent the current best thinking from leading researchers and clinicians.
This is not a casual supplement you add to your morning routine. It's a prescription medication that requires medical supervision, regular monitoring, and informed decision-making. For those willing to do the work, it may represent the single most impactful pharmacological longevity intervention available today.
This article is for informational purposes only and does not constitute medical advice. Rapamycin is a prescription medication — always work with a qualified physician.