The mechanistic (or mammalian) target of rapamycin (mTOR) is a well studied portion of cellular biochemistry. The activity of mTOR and downstream consequences of that activity form one portion of a broad regulatory system that reacts to nutrient availability in order to change growth and stress responses in cells. Inhibition of mTOR is a necessary part of the beneficial response to fasting and calorie restriction, in which an increase in the activity of cell maintenance processes acts to improve health and slow the progression of aging. Animal studies robustly demonstrate extended lifespan in response to mTOR inhibition. In recent years a number of programs have focused on the development of novel drugs targeting mTOR, while the generic mTOR inhibitor rapamycin is widely employed by anti-aging clinics, and was the subject of a community-funded clinical trial.
Aging is a highly intricate biochemical process. There is strong evidence suggesting that organismal aging, age-dependent diseases, and cellular senescence are related to the mammalian target of rapamycin (mTOR) signaling pathway. The signaling pathway of mTOR has become a prominent regulatory hub, managing crucial cellular activities that significantly affect lifespan and longevity. The mTOR is involved in controlling cell growth and metabolism in response to both internal and external energy signals as well as growth factors. The interaction between mTOR and cellular homeostasis is crucial in the aging process.
This extensive review summarizes the most recent findings on mTOR inhibitors in the context of aging, highlighting their complex interactions with cellular systems, effect on longevity, and potential as therapeutic approaches for age-related diseases. Rapamycin and rapalogs (analogs of rapamycin), which have been proven to be effective mTOR inhibitors, have the ability to reduce the aging process in several model species while also enhancing metabolic health and stress responses.
These results suggest mTOR inhibitors as potential therapies to address the complex aspects of age-related diseases. However, obstacles stand in the way of clinical translation. Further research is required to improve dosing protocols, reduce potential side effects, and target mTOR inhibitors precisely at specific tissues.
Link: https://doi.org/10.17179/excli2025-8384
View the full article at FightAging
