Journal
CELL METABOLISM
Volume 23, Issue 6, Pages 990-1003Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2016.05.009
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Funding
- NIH [R56 AG050441]
- K99/R00 Pathway to Independence Award [R00 AG041765]
- Wisconsin Partnership Program
- Glenn Foundation Award for Research in the Biological Mechanisms of Aging
- UW-Madison School of Medicine and Public Health
- UW-Madison Department of Medicine
- American Federation for Aging Research
- Delos Pharmaceuticals
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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.
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