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Rapalogs and mTOR inhibitors as anti-aging therapeutics
Dudley W. Lamming, … , David M. Sabatini, Joseph A. Baur
Dudley W. Lamming, … , David M. Sabatini, Joseph A. Baur
Published March 1, 2013
Citation Information: J Clin Invest. 2013;123(3):980-989. https://doi.org/10.1172/JCI64099.
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Review Series

Rapalogs and mTOR inhibitors as anti-aging therapeutics

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Abstract

Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has the strongest experimental support to date as a potential anti-aging therapeutic in mammals. Unlike many other compounds that have been claimed to influence longevity, rapamycin has been repeatedly tested in long-lived, genetically heterogeneous mice, in which it extends both mean and maximum life spans. However, the mechanism that accounts for these effects is far from clear, and a growing list of side effects make it doubtful that rapamycin would ultimately be beneficial in humans. This Review discusses the prospects for developing newer, safer anti-aging therapies based on analogs of rapamycin (termed rapalogs) or other approaches targeting mTOR signaling.

Authors

Dudley W. Lamming, Lan Ye, David M. Sabatini, Joseph A. Baur

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Figure 2

Chronic rapamycin treatment disrupts mTORC2.

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Chronic rapamycin treatment disrupts mTORC2.
(A) In vivo, nutrients and ...
(A) In vivo, nutrients and growth factors drive the activity of mTORC1 and mTORC2, which promote growth, aging, and insulin sensitivity. (B) Acute treatment with rapamycin inhibits mTORC1 signaling, restricting growth and promoting longevity without reducing insulin sensitivity. (C) Chronic treatment with rapamycin inhibits both mTORC1 and mTORC2, restricting growth and impairing insulin signaling, but promoting longevity.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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