Rapamycin (Sirolimus) is an FDA-approved drug initially used to prevent organ transplant rejection and treat certain cancers¹. It has garnered interest for its potential off-label use to extend lifespan and improve healthspan based on preclinical studies in yeast, invertebrates, and rodents¹².

Potential Benefits:

1. Longevity: Rapamycin has been shown to increase lifespan in various organisms, including mammals²³. It likely achieves this by inhibiting the mTOR pathway, which is involved in cell growth, proliferation, protein synthesis, and autophagy.

2. Anti-Aging: Its anti-aging properties include reducing the occurrence of age-related diseases and potentially improving age-related cognitive impairments³.

3. Anti-Inflammatory: Rapamycin has notable anti-inflammatory effects, which might contribute to its ability to ameliorate some aging-related conditions⁴.

Potential Side Effects:

1. Metabolic Effects: Long-term use of rapamycin can lead to lipid metabolism disorders, such as fatty liver and hyperlipidemia⁴.

2. Immune Modulation: As an immunosuppressant, it may increase susceptibility to infections⁵.

3. Liver Toxicity: Although rapamycin can induce fatty liver, studies suggest this type of fatty liver may not be as harmful as diet or alcohol-induced fatty liver⁴.

Clinical and Off-Label Use:

• Physicians have started prescribing rapamycin off-label for its potential to enhance healthspan, although there is limited data on its long-term safety and efficacy in this context¹.
• It has also been explored in combination with other drugs like acarbose, showing significant increases in lifespan in animal studies⁵.

Considerations:

• Dosing: The appropriate dosing regimen for anti-aging benefits is not fully established and might vary depending on individual health conditions.
• Medical Guidance: Due to potential side effects and immunosuppressive properties, rapamycin should only be used under medical supervision.

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Footnotes

1. Evaluation of off-label rapamycin use to promote healthspan in 333 adults - PubMed ↩ ↩² ↩³

2. Longevity, aging and rapamycin ↩ ↩²

3. Rapamycin, the only drug that consistently demonstrated to increase mammalian longevity. An update ↩ ↩²

4. Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers ↩ ↩² ↩³

5. Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice ↩ ↩²