title: Inhibition of the Mechanistic Target of Rapamycin (mTOR)-Rapamycin and Beyond.
abstract: Rapamycin is a Food and Drug Administration (FDA)-approved immunosuppressant and anticancer agent discovered in the soil of Easter Island in the early 1970s. Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, which acts as a central integrator of nutrient signaling pathways. During the last decade, genetic and pharmaceutical inhibition of mTOR pathway signaling has been found to promote longevity in yeast, worms, flies, and mice. In this article, we will discuss the molecular biology underlying the effects of rapamycin and its physiological effects, evidence for rapamycin as an antiaging compound, mechanisms by which rapamycin may extend life span, and the potential limitations of rapamycin as an antiaging molecule. Finally, we will discuss possible strategies that may allow us to inhibit mTOR signaling safely while minimizing side effects, and reap the health, social, and economic benefits from slowing the aging process.
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison and William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.
authors.forename: Dudley W
authors.initials: DW
authors.lastname: Lamming
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008136:Longevity / Q000187:drug effects*; D051379:Mice; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus