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 al...

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Bibliographic Details
Published in:Cell metabolism 2016-06, Vol.23 (6), p.990-1003
Main Authors: Kennedy, Brian K., Lamming, Dudley W.
Format: Article
Language:English
Subjects:
Aging - metabolism
Animals
Humans
Metabolism
Organ Specificity
Signal Transduction
Substrate Specificity
TOR Serine-Threonine Kinases - metabolism
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Summary: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. In this Review Article, Kennedy and Lamming highlight recent findings regarding the central role of the mechanistic target of rapamycin (mTOR), a protein kinase regulated by many growth factors and environmental cues, in the regulation of organismal metabolism and aging.
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2016.05.009