Rapamycin Lifespan Extension

Rapamycin is a macrolide compound derived from Streptomyces hygroscopicus. It is a well-known immunosuppressant and antibiotic drug that has shown promise in extending the lifespan of animal species, particularly when administered in mid-life. Rapamycin inhibits the mechanistic target of rapamycin (mTOR), a regulator of cellular growth and metabolism.

The drug has been researched in various species, showing promise in rodents, nematodes, fruit flies, and yeast. Studies in mice have demonstrated lifespan extensions of 9%-14% and 39-61% with rapamycin treatment.

mTOR inhibition, also via caloric restriction and intermittent fasting, enhances lifespan and healthspan by shifting cellular activity towards maintenance and repair. This process improves proteostasis and reduces cellular 'toxic burden'.

The Test of Rapamycin in Aging Dogs (TRIAD) trial investigates rapamycin's effects on dogs' lifespan and healthspan, as dogs share many age-related diseases and physiological similarities with humans.

However, the translational efficacy of rapamycin in humans for extending lifespan remains unclear due to side effects and the complexity of aging. Short-term rapamycin trials in humans have indicated some positive effects on immune function. However, the focus is on understanding the complex side effects, long-term implications, and ethical considerations of rapamycin use.

While mTOR inhibition shows promise, challenges regarding side effects, ethical considerations, and the intricate interplay of the pathway with nutrient metabolism and the microbiome must be addressed.

In summary, rapamycin is a potent mTOR inhibitor with a strong preclinical basis for lifespan extension and a proven clinical benefit in specific genetic disorders. However, its use for general anti-aging in humans is fraught with challenges related to efficacy, safety, side effects, ethical considerations, and the need for robust clinical evidence and standardized biomarkers.