Next Generation Strategies for Geroprotection via mTORC1 Inhibition.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Sabrina N Dumas, Dudley W Lamming

Abstract

Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) with the pharmaceutical rapamycin prolongs the lifespan and healthspan of model organisms including rodents, with evidence now emerging that rapamycin and its analogs may also have rejuvenative effects in dogs and humans. However, the side effects associated with long-term rapamycin treatment, many of which are due to inhibition of a second mTOR complex, mTORC2, have seemed to preclude the routine use of rapamycin as a therapy for age-related diseases. Here, we discuss recent findings suggesting that strong, chronic inhibition of both mTOR complexes may not be necessary to realize the geroprotective effects of rapamycin. Instead, modestly but specifically inhibiting mTORC1 via a variety of emerging techniques, including intermittent or transient treatment with rapamycin derivatives, or specific dietary regimens, may be sufficient to promote health and longevity with reduced side effects. We will also discuss prospects for the development of new molecules that, by harnessing the detailed molecular understanding of mTORC1 signaling developed over the last decade, will provide new routes to the selective inhibition of mTORC1. We conclude that therapies based on the s...Continue Reading

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Citations

Feb 23, 2019·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Sabrina N Dumas, Dudley W Lamming
Aug 2, 2019·Cell Cycle·Mikhail V Blagosklonny
Sep 24, 2019·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Dudley W Lamming, Adam B Salmon
Nov 7, 2019·Aging Cell·Candice E Van SkikeVeronica Galvan
Jan 10, 2020·Nature Protocols·I BellantuonoD W Lamming
Aug 3, 2019·Aging Cell·Karthikeyani ChellappaDudley W Lamming
Jul 22, 2019·Nature Communications·Katherine H SchreiberDudley W Lamming
Oct 11, 2020·GeroScience·Ramasamy SelvaraniArlan Richardson
Jun 1, 2021·Frontiers in Immunology·Miguel Ángel Palacios-PedreroGiulietta Saletti
Jul 16, 2021·Translational Medicine of Aging·Reji Babygirija, Dudley W Lamming
Oct 13, 2021·Developmental Cell·Chung-Yang Yeh, Dudley W Lamming

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