Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction
© 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...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/134061 |
| _version_ | 1826197327647342592 |
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| author | 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 Jasper, Henri Yilmaz, Ömer H Ori, Alessandro |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT 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 Jasper, Henri Yilmaz, Ömer H Ori, Alessandro |
| author_sort | Gebert, Nadja |
| collection | MIT |
| description | © 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. |
| first_indexed | 2024-09-23T10:45:59Z |
| format | Article |
| id | mit-1721.1/134061 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:45:59Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1340612023-12-08T21:42:51Z Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction 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 Jasper, Henri Yilmaz, Ömer H Ori, Alessandro Koch Institute for Integrative Cancer Research at MIT © 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. 2021-10-27T19:57:53Z 2021-10-27T19:57:53Z 2020 2021-08-05T14:39:35Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134061 en 10.1016/J.CELREP.2020.107565 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | 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 Jasper, Henri Yilmaz, Ömer H Ori, Alessandro Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction |
| title | Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction |
| title_full | Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction |
| title_fullStr | Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction |
| title_full_unstemmed | Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction |
| title_short | Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction |
| title_sort | region specific proteome changes of the intestinal epithelium during aging and dietary restriction |
| url | https://hdl.handle.net/1721.1/134061 |
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