Rapamycin’s mechanism of action involves inhibiting the mechanistic target of rapamycin (mTOR), a protein kinase that plays a crucial role in regulating cell growth, proliferation, metabolism, and aging. mTOR exists in two distinct complexes, mTORC1 and mTORC2. mTORC1 is more sensitive to rapamycin and is responsible for controlling cell growth and metabolism. mTORC2, on the other hand, is involved in the regulation of cytoskeletal organization, cell survival, and cell metabolism.

Inhibition of mTORC1 by Rapamycin has been shown to have several beneficial effects on age-related diseases and longevity. These include:

1. Prolonging lifespan: Studies in yeast, worms, flies, and mice have demonstrated that rapamycin treatment can increase lifespan. In mice, rapamycin supplementation has been shown to extend median and maximum lifespan by up to 14% in females and 9% in males.
2. Delaying aging: Rapamycin has been found to slow down the aging process by reducing age-related damage to cells, improving cellular function, and promoting cellular repair mechanisms.
3. Improving age-related diseases: Rapamycin has been shown to improve various age-related diseases and conditions, such as diabetes, cardiovascular disease, and neurodegenerative diseases like Alzheimer’s and Parkinson’s.

The exact mechanisms by which rapamycin exerts its anti-aging effects are not fully understood, but several hypotheses have been proposed. Some of these include:

1. Autophagy enhancement: Rapamycin has been shown to enhance autophagy, a cellular process that helps remove damaged or dysfunctional organelles and proteins, which can contribute to aging.
2. mTORC1-mediated metabolic regulation: Inhibition of mTORC1 by Rapamycin leads to changes in cellular metabolism, including reduced insulin signaling, increased fat oxidation, and reduced inflammation, all of which may contribute to the anti-aging effects.
3. Telomere maintenance: Rapamycin has been shown to maintain telomere length, which can help protect against cellular aging.

While Rapamycin shows great promise as an anti-aging therapy, there are still challenges to overcome before it can be widely used in humans. Some of these challenges include:

1. Side effects: Rapamycin has been shown to have side effects in animals, including immunosuppression, gastrointestinal issues, and impaired glucose tolerance. These side effects need to be carefully evaluated in human clinical trials.
2. Dose and timing: The optimal dose and timing of Rapamycin administration for anti-aging effects are not yet established and may need to be tailored to individual patients.
3. Drug delivery: Rapamycin is typically administered orally or intraperitoneally, but alternative drug delivery methods may be needed for more effective and targeted treatment.

Despite these challenges, ongoing research and clinical trials are exploring the potential of Rapamycin as an anti-aging therapy. With further research, Rapamycin may become an important tool in the fight against aging and age-related diseases. However, compared to other nutrients that are essential parts of our Longevity Lifestyle, we remain cautious in the case of Rapamycin because of the above mentioned complexity, specifically regarding potential side effects and dosing.

If you want to learn even more about Rapamycin, you might want to watch this podcast episode by Peter Attia, in conversation with longevity researchers Matt Kaeberlein and David Sabatini.