What are the protocols for using rapamycin (sirolimus) for longevity?

Rapamycin Protocols for Longevity

Currently, there are no FDA-approved protocols for using rapamycin (sirolimus) specifically for longevity purposes, and its use for this indication remains off-label and experimental.

Current Evidence and Dosing Considerations

Dosing Regimens

Based on available evidence, intermittent dosing appears to be the most promising approach for longevity benefits while minimizing side effects:

• Intermittent dosing: 2mg/kg administered every 5 days has shown life span extension in female C57BL/6J mice with reduced metabolic and immunological side effects compared to daily dosing 1
• Weekly dosing: Alternating weekly administration of rapamycin with control periods has demonstrated lifespan extension in animal models while partially ameliorating glucose intolerance side effects 2
• Low-dose options: For adults, starting doses of 1mg once weekly is common in off-label use, with careful monitoring 3

Monitoring Requirements

When using mTOR inhibitors like rapamycin, the following monitoring is recommended:

• Before treatment initiation:

  • Baseline cholesterol and triglyceride levels 4
  • Complete blood count (CBC) 4
  • Renal function (creatinine) 4
  • Blood pressure measurement 4

• During treatment:

  • Regular monitoring of drug concentration 4
  • Ongoing hyperlipidemia monitoring 4
  • CBC, creatinine, and blood pressure monitoring 4
  • Blood glucose levels to detect potential metabolic effects 2

Contraindications and Precautions

• Avoid in patients with:

  • Abnormal elevation of fasting triglycerides 4
  • Poor wound healing risk 4
  • Active infections 4
  • Renal insufficiency 4

• Discontinue temporarily during:

  • Infections 4
  • Surgical procedures (due to poor wound healing risk) 4

Potential Benefits and Side Effects

Potential Benefits

• Extends lifespan in multiple animal models 4, 2
• May improve aspects of healthspan 2
• Enhances autophagy, which becomes dysfunctional with aging 4

Common Side Effects

• Hyperlipidemia (elevated cholesterol and triglycerides) 4
• Glucose intolerance 2
• Mouth ulcers
• Increased risk of infections 4
• Potential pulmonary toxicity (monitor for new respiratory symptoms) 4

Practical Protocol Considerations

For those considering off-label use for longevity purposes (with physician supervision):

1. Initial evaluation:

   • Complete health assessment including lipid panel, CBC, comprehensive metabolic panel
   • Exclude contraindications and assess risk factors

2. Starting protocol:

   • Begin with low dose (1mg weekly) and monitor for side effects
   • Consider intermittent dosing (e.g., one week on, one week off) to minimize side effects while maintaining benefits 2

3. Monitoring protocol:

   • Check lipid levels and blood glucose every 3 months initially
   • Monitor CBC and renal function regularly
   • Assess for any respiratory symptoms that could indicate pulmonary toxicity 4

4. Dose adjustments:

   • Consider dose reduction if side effects occur
   • Temporary discontinuation during infections or surgical procedures

Important Caveats

• The evidence for rapamycin's effects on human longevity remains preliminary and largely based on animal studies
• Current human use for longevity is considered experimental and off-label
• The optimal dosing regimen for humans specifically targeting longevity has not been established in clinical trials
• Long-term safety data for low-dose intermittent use in otherwise healthy individuals is limited 3

While rapamycin shows promise as a potential longevity intervention based on animal studies, its use for this purpose should be approached with caution and under close medical supervision given the lack of established protocols and potential side effects.