The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging.
Since the discovery that rapamycin, a small molecule inhibitor of the protein kinase mTOR (mechanistic target of rapamycin), can extend the lifespan of model organisms including mice, interest in understanding the physiological role and molecular targets of this pathway has surged. While mTOR was already well known as a regulator of growth and protein translation, it is now clear that mTOR functions as a central coordinator of organismal metabolism in response to both environmental and hormonal signals. This review discusses recent developments in our understanding of how mTOR signaling is regulated by nutrients and the role of the mTOR signaling pathway in key metabolic tissues. Finally, we discuss the molecular basis for the negative metabolic side effects associated with rapamycin treatment, which may serve as barriers to the adoption of rapamycin or similar compounds for the treatment of diseases of aging and metabolism.
The Buck Institute for Research on Aging, Novato, CA 94945, USA.
Brian K
BK
Kennedy
Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA. Electronic address: dlamming@medicine.wisc.edu.
Dudley W
DW
Lamming
D000375:Aging / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008660:Metabolism; D009928:Organ Specificity; D015398:Signal Transduction; D013379:Substrate Specificity; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D058570:TOR Serine-Threonine Kinases