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

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 3

Metformin regulates mTORC1 signaling.

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Metformin regulates mTORC1 signaling. Metformin activates AMPK by inhibi...
Metformin activates AMPK by inhibiting oxidative phosphorylation, which in turn negatively regulates mTORC1 signaling via activation of TSC2 and inhibitory phosphorylation of raptor. In parallel, metformin inhibits mTORC1 signaling by suppressing the activity of the Rag GTPases and upregulating REDD1.