Calorie Restriction Governs Intestinal Epithelial Regeneration through Cell-Autonomous Regulation of mTORC1 in Reserve Stem Cells

Stem Cell Reports
Maryam YousefiChristopher J Lengner

Abstract

Aging is a complex process associated with a decline in functionality of adult stem cells affecting tissue homeostasis and regeneration. Calorie restriction (CR) is the only experimental manipulation known to extend lifespan and reduce the incidence of age-related disorders across numerous species. These benefits are likely mediated, at least in part, through the preservation of stem cell function. Here, we show that CR enhances the regenerative capacity of the intestinal epithelium through preservation of an injury-resistant reserve intestinal stem cell (ISC) pool. Cell-autonomous activity of mechanistic target of rapamycin complex 1 (mTORC1) governs the sensitivity of reserve ISCs to injury. CR inhibits mTORC1 in these cells, protecting them against DNA damage, while mTORC1 stimulation, either genetically or through nutrient sensing, sensitizes reserve ISCs to injury, thus compromising regeneration of the epithelium. These data delineate a critical role for mTORC1 in epithelial regeneration and inform clinical strategies based on nutrient modulation.

Citations

Feb 5, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Liara M GonzalezAnthony T Blikslager
Apr 5, 2019·Cellular and Molecular Life Sciences : CMLS·Harleen Kaur, Régis Moreau
Oct 15, 2019·Annual Review of Physiology·Heinrich Jasper
Jun 23, 2020·EMBO Reports·Maja C FunkMichael Boutros
Sep 2, 2018·Disease Models & Mechanisms·Joseph Burclaff, Jason C Mills
Oct 18, 2018·Nature Reviews. Cancer·Alessio NencioniValter D Longo
Jan 4, 2020·Nature Communications·Dan HeBaojie Li
Jul 22, 2019·Human Genetics·Taylor McNeelyIsabel Beerman
Sep 6, 2020·International Journal of Molecular Sciences·Aurélia Joly, Raphaël Rousset
Nov 18, 2020·Stem Cell Reviews and Reports·Shao-Jie LiangXiu-Qi Wang
Feb 16, 2021·Stem Cell Reviews and Reports·Hélia FernandesEugénia Carvalho
Jun 24, 2020·Mechanisms of Ageing and Development·Svenja C SchülerAlessandro Ori
Mar 22, 2021·Aging·Kavitha KurupArchana Unnikrishnan
Aug 26, 2020·Developmental Cell·Joris H HagemanHugo J G Snippert
Jul 1, 2021·Cold Spring Harbor Perspectives in Biology·Thomas A Rando, D Leanne Jones
Oct 8, 2021·Biological Reviews of the Cambridge Philosophical Society·Baruch RinkevichBert Hobmayer
Oct 28, 2020·Developmental Cell·Nicolette M Johnson, Christopher J Lengner

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence-activated cell sorting

Software Mentioned

GSEA

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.