Review
Version 1
Preserved in Portico This version is not peer-reviewed
Rapamycin and Rapalogs
Version 1
: Received: 21 February 2021 / Approved: 22 February 2021 / Online: 22 February 2021 (15:34:25 CET)
How to cite: Lamming, D. Rapamycin and Rapalogs. Preprints 2021, 2021020491. https://doi.org/10.20944/preprints202102.0491.v1 Lamming, D. Rapamycin and Rapalogs. Preprints 2021, 2021020491. https://doi.org/10.20944/preprints202102.0491.v1
Abstract
Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) signaling promotes health and longevity in diverse model organisms. Over the past decade, excitement has built over the possibility that treatment with the mTORC1 inhibitor rapamycin can be utilized to treat or prevent age-related disease in humans. However, concerns over the side effects of rapamycin on immunity and metabolism have precluded the routine use of rapamycin as a geroprotective therapy. Here, we discuss the evidence that these negative side effects of rapamycin are largely mediated by off-target inhibition of a second mTOR Complex (mTORC2). Further, we discuss how intermittent treatment with rapamycin, specific dietary regimens, and new molecules may provide routes to the safer and more selective inhibition of mTORC1. We conclude that the time is ripe for the development of therapies based on the safe and selective inhibition of mTORC1 for the treatment or prevention of diseases of aging.
Keywords
mTORC1; mTORC2; rapamycin; rapalog; aging; lifespan; longevity
Subject
Biology and Life Sciences, Anatomy and Physiology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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