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Publication : Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction.

First Author  Gebert N Year  2020
Journal  Cell Rep Volume  31
Issue  4 Pages  107565
PubMed ID  32348758 Mgi Jnum  J:299256
Mgi Id  MGI:6488839 Doi  10.1016/j.celrep.2020.107565
Citation  Gebert N, et al. (2020) Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction. Cell Rep 31(4):107565
abstractText  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.
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