Dataset Information

Region-specific proteome changes of the intestinal epithelium during aging and dietary restriction

ABSTRACT: The small intestine is responsible for nutrient absorption and it is one of the most important interfaces between the environment and our body. During aging, changes in the structure of the epithelium lead to food malabsorption and reduced barrier function thus increasing disease risk in aging. The molecular drivers of these alterations remain poorly understood. Here, we compared the proteomes of small intestinal crypts from mice across different anatomical regions and age groups. We found that aging alters epithelial immune responses, metabolic networks and stem cell proliferation, and it is accompanied by a region-dependent skewing in the cellular composition of the intestinal epithelium. Of note, a short period of dietary restriction followed by re-feeding partially restores the epithelium to a youthful state by promoting the differentiation of intestinal stem cells (ISCs) towards the secretory lineage. Using in vitro and in vivo studies, we identify Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthetase 2) – the rate limiting enzyme in the synthesis of ketone bodies – as a modulator of ISCs differentiation, which responds to dietary changes. This study provides an atlas of age-dependent proteome changes in defined regions of the intestinal epithelium and characterizes how young and old mice adapt to drastic changes of diet, such as dietary restriction and re-feeding.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Small Intestine Epithelium

SUBMITTER: Alessandro Ori

LAB HEAD: Alessandro Ori

PROVIDER: PXD014311 | Pride | 2020-04-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	160401_NG_crypts_sample12_DIA_750ng1.raw	Raw
	160401_NG_crypts_sample12_DIA_750ng2.raw	Raw
	160408_NG_crypts_DIA_sample1.raw	Raw
	160408_NG_crypts_DIA_sample10.raw	Raw
	160408_NG_crypts_DIA_sample10_160411200157.raw	Raw

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Publications

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

Gebert Nadja N Cheng Chia-Wei CW Kirkpatrick Joanna M JM Di Fraia Domenico D Yun Jina J Schädel Patrick P Pace Simona S Garside George B GB Werz Oliver O Rudolph K Lenhard KL Jasper Henri H Yilmaz Ömer H ÖH Ori Alessandro A

Cell reports 20200401 4

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 ...[more]

PMID: 32348758

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