Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction.
aging
dietary restriction
hmgcs2
intestine
ketone bodies
proteomics
stem cells
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
28 04 2020
28 04 2020
Historique:
received:
17
09
2019
revised:
05
02
2020
accepted:
02
04
2020
entrez:
30
4
2020
pubmed:
30
4
2020
medline:
14
5
2021
Statut:
ppublish
Résumé
The small intestine is responsible for nutrient absorption and one of the most important interfaces between the environment and the body. During aging, changes of the epithelium lead to food malabsorption and reduced barrier function, thus increasing disease risk. The drivers of these alterations remain poorly understood. Here, we compare the proteomes of intestinal crypts from mice across different anatomical regions and ages. We find that aging alters epithelial immunity, metabolism, and cell proliferation and is accompanied by region-dependent skewing in the cellular composition of the epithelium. Of note, short-term dietary restriction followed by refeeding partially restores the epithelium by promoting stem cell differentiation toward the secretory lineage. We identify Hmgcs2 (3-hydroxy-3-methylglutaryl-coenzyme A [CoA] synthetase 2), the rate-limiting enzyme for ketogenesis, as a modulator of stem cell differentiation that responds to dietary changes, and we provide an atlas of region- and age-dependent proteome changes of the small intestine.
Identifiants
pubmed: 32348758
pii: S2211-1247(20)30514-3
doi: 10.1016/j.celrep.2020.107565
pmc: PMC7446723
mid: NIHMS1612178
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107565Subventions
Organisme : NCI NIH HHS
ID : R01 CA245314
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK123407
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA034992
Pays : United States
Organisme : NIDDK NIH HHS
ID : K99 DK123407
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224068
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211184
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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