Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction
Name
1-s2.0-S2211124720305143-main.pdf
Description
Published version
Size
7.51 MB
Format
Adobe PDF
Checksum (MD5)
4acc80b34fe2e73a4abf6f8c0c873392
Author(s)
Gebert, Nadja
Cheng, Chia-Wei
Kirkpatrick, Joanna M
Di Fraia, Domenico
Yun, Jina
Schädel, Patrick
Pace, Simona
Garside, George B
Werz, Oliver
Rudolph, K Lenhard
Date Issued
2020
Journal
Cell Reports
Publisher
Elsevier BV
Version
Final published version
Abstract
© 2020 The Author(s) 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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELREP.2020.107565
