Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice
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Calorie restriction (CR) promotes healthy ageing in diverse species. Recently, it has been shown that fasting for a portion of each day has metabolic benefits and promotes lifespan. These findings complicate the interpretation of rodent CR studies, in which animals typically eat only once per day and rapidly consume their food, which collaterally imposes fasting. Here we show that a prolonged fast is necessary for key metabolic, molecular and geroprotective effects of a CR diet. Using a series of feeding regimens, we dissect the effects of calories and fasting, and proceed to demonstrate that fasting alone recapitulates many of the physiological and molecular effects of CR. Our results shed new light on how both when and how much we eat regulate metabolic health and longevity, and demonstrate that daily prolonged fasting, and not solely reduced caloric intake, is likely responsible for the metabolic and geroprotective benefits of a CR diet.
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Prolonged fasting of 10 months resulted in caloric restriction-mediated increase in insulin sensitivity.
“prolonged fasting of 10 months resulted in caloric restriction–mediated increase in insulin sensitivity.”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [60]
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The Rhesus Macaque as an Animal Model for Human Nutrition: An Ecological-Evolutionary Perspective
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- Authors
- Pak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., Yang, S. E., Dumas, S. N., Sonsalla, M., Bray, L., Johnson, M., Barnes, S., Darley-Usmar, V., Zhang, J., Yen, C.-L. E., Denu, J. M., & Lamming, D. W.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Lamming, Dudley W.
- ORCID
- Venue
- Nature Metabolism
- Published
- 2021-10-18
- Volume
- 3
- Issue
- 10
- Pages
- 1327-1341
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC8544824
- OpenAlex
- W3205401845
- Cited by
- 171
- References
- 79
- Citations by year
- 2026: 19 · 2025: 37 · 2024: 38 · 2023: 42 · 2022: 29 · 2021: 6
- FWCI
- 18.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (AG066311, AG056771, T32 AG000213, P30AG050886, AG050135, AG051974, AG062328, AG061635)
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK007665, DK124696, DK125859)
- American Federation for Aging Research
- U.S. Department of Veterans Affairs (I01-BX004031)
- U.S. Department of Health & Human Services | NIH | NIH Office of the Director (S10OD028739)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R37GM059785)
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- caloric restriction, fasting, healthy aging, lifespan extension, prolonged fasting, feeding regimen, metabolic health, geroprotective effects, meal timing, energy intake
- MeSH terms
- Aging, Animals, Longevity, Caloric Restriction, Mice
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