Cited by 172Dietary Effects on HealthGenetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in Medicine

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Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice

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Pak, Heidi H., Haws, Spencer A., Green, Cara L., Koller, Mikaela, Lavarias, Mitchell T., Richardson, Nicole E., Yang, Shany E., Dumas, Sabrina N., Sonsalla, Michelle, Bray, Lindsey, Johnson, Michelle, Barnes, Stephen, Darley-Usmar, Victor, Zhang, Jianhua, Yen, Chi-Liang Eric, Denu, John M., Lamming, Dudley W.·2021·Nature Metabolism

DOI 10.1038/s42255-021-00466-9PMC PMC8544824

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Abstract

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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Velingkaar, N., Astaf’ev, A. A., Prabahar, A., Maravillas, M. A., Trokhimenko, E., Rom, J.-M. B., Asi, G. J., Piontkivska, H., Jiang, P., & Kondratov, R. V. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118022
Cancer Cell Metabolic Reprogramming: Dietary, Pharmacological Strategies and Clinical Perspectives
Xydas, N., Panagiotou, Ε., Kassos, V., Gkirmpa, A. M., Kassou, P., Voyiatzis, I., Prenti, P., Manias, G., Vakrakou, A. G., & Anagnostopoulos, A. K. (2026) · Cancers · doi:10.3390/cancers18203372
The Role of Physical Activity and Diet in Regulating Aging: From Universal Mechanisms to Personalized Longevity Strategies
Egorova, E. S., & Ahmetov, I. I. (2026) · Advances in Gerontology · doi:10.1134/s2079057026600424

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: Pak, Heidi H.
Haws, Spencer A.
Green, Cara L.
Lavarias, Mitchell T.
Richardson, Nicole E.
Yang, Shany E.
Dumas, Sabrina N.
Sonsalla, Michelle
Barnes, Stephen
Darley-Usmar, Victor
Zhang, Jianhua
Yen, Chi-Liang Eric
Denu, John M.
Lamming, Dudley W.
Venue: Nature Metabolism
Publisher: Springer Science and Business Media LLC
Published: 2021-10-18
Volume: 3
Issue: 10
Pages: 1327-1341
ISSN: 2522-5812 (ISSN-L)
DOI: 10.1038/s42255-021-00466-9
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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 (medical) › 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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Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice

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