Region-Specific Proteome Changes of the Intestinal Epithelium during Aging and Dietary Restriction
Open accessAbstract
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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HMGCS2 impacts cell fate decisions of the stem cell.
“The levels of the rate-limiting enzyme for ketogenesis, 3-hydroxy-3-methylglutaryl coenzyme A synthetase 2 (HMGCS2), are increased with dietary restriction and impact cell fate decisions of the stem cell211.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [211]
Dietary restriction can generally reprogramme both the transcriptome and the proteome in ageing rats and mice.
“Dietary restriction can generally ‘reprogramme’ both the transcriptome and the proteome in ageing rats and mice210,211.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [211]
Dietary restriction followed by refeeding restores aged epithelial function by promoting stem cell differentiation along the secretory lineage.
“Dietary restriction followed by refeeding restores aged epithelial function by promoting stem cell differentiation along the secretory lineage211.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [211]
Levels of the rate-limiting enzyme for ketogenesis, HMGCS2, are increased with dietary restriction.
“The levels of the rate-limiting enzyme for ketogenesis, 3-hydroxy-3-methylglutaryl coenzyme A synthetase 2 (HMGCS2), are increased with dietary restriction and impact cell fate decisions of the stem cell211.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [211]
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Ageing and rejuvenation of tissue stem cells and their niches
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- Authors
- Gebert, N., Cheng, C.-W., Kirkpatrick, J. M., Di Fraia, D., Yun, J., Schädel, P., Pace, S., Garside, G. B., Werz, O., Rudolph, K. L., Jasper, H., Yilmaz, Ö. H., & Ori, A.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Genentech (US)
- Friedrich Schiller University Jena (DE)
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 31
- Issue
- 4
- Pages
- 107565
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7446723
- OpenAlex
- W3018757751
- Cited by
- 88
- References
- 51
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 14 · 2023: 14 · 2022: 10 · 2021: 13 · 2020: 8
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc-nd)
- Funders
- Deutsches Zentrum für Herz-Kreislaufforschung (81X2800193)
- Else Kröner-Fresenius-Stiftung (2019_A79)
- Deutsche Forschungsgemeinschaft (GRK 2155)
- Leibniz-Gemeinschaft
- National Institutes of Health (R01CA211184, K99 DK123407-01, R00 AG045144, U54CA224068, R01CA034992, SFB1127 ChemBioSys)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- intestinal epithelium, aging, dietary restriction, refeeding, small intestine, intestinal crypts, regional heterogeneity, epithelial immunity, epithelial metabolism, cell proliferation, intestinal stem cells, HMGCS2, ketogenesis, epithelial barrier function
- MeSH terms
- Age Factors, Animals, Diet Therapy, Humans, Intestinal Mucosa, Proteomics, Mice
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