Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging
Open accessAbstract
Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting. Acute genetic disruption of Cpt1a, the rate-limiting enzyme in FAO, abrogates ISC-enhancing effects of fasting, but long-term Cpt1a deletion decreases ISC numbers and function, implicating a role for FAO in ISC maintenance. These findings highlight a role for FAO in mediating pro-regenerative effects of fasting in intestinal biology, and they may represent a viable strategy for enhancing intestinal regeneration.
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CPT1A is necessary for the improvement of ISCs upon fasting.
“Indeed, the critical enzyme for fatty acid oxidation, carnitine palmitoyltransferase 1A (CPT1A), is necessary for this improvement of ISCs upon fasting214.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [214]
The beneficial effect of fasting on ISCs is in part mediated by the induction of fatty acid oxidation.
“The beneficial effect of fasting on ISCs is in part mediated by the induction of fatty acid oxidation214.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [214]
Complete fasting (nutrient deprivation for 24 h) has beneficial effects on intestinal stem cell (ISC) function in both young and old mice.
“Interestingly, complete fasting (nutrient deprivation for 24 h) has beneficial effects on ISC function — measured in this case by the ability of ISCs to regenerate in organoids — in both young mice and old mice214.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [214]
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- Authors
- Mihaylova, M. M., Cheng, C.-W., Cao, A. Q., Tripathi, S., Mana, M. D., Bauer-Rowe, K. E., Abu-Remaileh, M., Clavain, L., Erdemir, A., Lewis, C. A., Freinkman, E., Dickey, A. S., La Spada, A. R., Huang, Y., Bell, G. W., Deshpande, V., Carmeliet, P., Katajisto, P., Sabatini, D. M., & Yilmaz, Ö. H.
- Affiliations
- Broad Institute (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Whitehead Institute for Biomedical Research (US)
- Duke University (US)
- Harvard University (US)
- KU Leuven (BE)
- University of Helsinki (FI)
- Corresponding author
- Sabatini, David M.
- Yilmaz, Ömer H.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 22
- Issue
- 5
- Pages
- 769-778.e4
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC5940005
- OpenAlex
- W2800440086
- Cited by
- 428
- References
- 60
- Citations by year
- 2026: 48 · 2025: 59 · 2024: 64 · 2023: 50 · 2022: 68 · 2021: 44 · 2020: 56 · 2019: 26 · 2018: 12
- FWCI
- 23.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- NIH (R00 AG045144, R01 CA211184, R01 CA034992, R01 CA103866, K99 AG054760, R01 AG033082, R01 NS065874)
- V Foundation V Scholar Award (6930750)
- Sidney Kimmel Scholar Award (6934241)
- Pew-Stewart Trust Scholar Award (025887-00001)
- Kathy and Curt Marble Cancer Research Fund
- American Federation of Aging Research (AFAR) (6932237)
- Glenn/AFAR Breakthroughs in Gerontology Award (6932237)
- Damon Runyon Postdoctoral Fellowship (DRG 2146-13)
- Ludwig Postdoctoral Fellowship (2036238)
- Helen Hay Whitney Postdoctoral Fellowship (16123046/ 2389185)
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- 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
- Keywords
- fasting, fatty acid oxidation, intestinal stem cells, CPT1A, intestinal regeneration, aging, tissue homeostasis, caloric restriction, stem cell maintenance
- MeSH terms
- Aging, Animals, Cells, Cultured, Fasting, Fatty Acids, Homeostasis, Intestines, Mice, Inbred Strains, Oxidation-Reduction, Stem Cells, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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