Noted biologist (and Editor-in-Chief of the journal Cell Cycle) Mikhail Blagosklonny reviews the biogerontology of the TOR (“Target Of Rapamycin”) pathway, and proposes that the eponymous drug rapamycin, aka sirolimus, might itself be useful as an anti-aging pharmaceutical.
Numerous mutations increase lifespan in diverse organisms from worms to mammals. Most genes that affect longevity encode components of the target of rapamycin (TOR) pathway, thus revealing potential targets for pharmacological intervention. I propose that one target, TOR itself, stands out, simply because its inhibitor (rapamycin) is a non-toxic, well-tolerated drug that is suitable for everyday oral administration. Preclinical and clinical data indicate that rapamycin is a promising drug for age-related diseases and seems to have anti-tumor, bone-sparing and calorie-restriction-mimicking ‘side-effects’. I also discuss other potential anti-aging agents (calorie restriction, metformin, resveratrol and sirtuins) and their targets, interference with the TOR pathway and combination with antioxidants.
I’m a little surprised that the author is proposing that rapamycin itself be used as an anti-aging drug: it’s an immune suppressant used to prevent transplant rejection, after all, and long-term immune suppression is usually considered one of the downsides of receiving a transplant. Furthermore, there are concerns that rapamycin can impair wound healing — another trait I wouldn’t look for in a chronically administered pharmaceutical.
Nonetheless, it’s a provocative idea, and the article provides a great many references to primary work describing the role (or possible role) for TOR in aging-related phenomena ranging from cellular senescence to calorie restriction.