Bench to bedside: is rapamycin headed for the docTOR?

Area of Science:

• Geroscience
• Pharmacology
• Molecular Biology

Background:

• Calorie restriction (CR) has long been known to extend lifespan and healthspan.
• Harnessing CR's mechanisms through pharmacological means is a key goal in aging research.
• Rapamycin, an inhibitor of the mechanistic Target Of Rapamycin (mTOR) pathway, has emerged as a significant geroprotector.

Purpose of the Study:

• To review the evolution of rapamycin from an immunosuppressant to a geroprotective agent.
• To summarize findings on rapamycin's benefits for longevity and organ function in model organisms.
• To discuss the clinical applications, challenges, and side-effects of rapamycin in humans.

Main Methods:

• Review of existing literature on rapamycin and mTOR inhibitors.
• Analysis of data from model organism studies on aging and longevity.
• Examination of completed and ongoing clinical trials in humans.

Main Results:

• Rapamycin demonstrates potent benefits for longevity and organ system function across various model organisms.
• Studies indicate rapamycin impacts key hallmarks of aging.
• Clinical trials are exploring rapamycin for age-related diseases, with ongoing evaluation of efficacy and safety.

Conclusions:

• Rapamycin is a reproducible pharmacological geroprotector with significant potential for extending healthspan and lifespan.
• Inhibition of the mTOR pathway by rapamycin or similar molecules may offer a path to achieving the long-sought goal of healthy aging.
• Challenges and side-effects require careful consideration for successful clinical translation.