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

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. +9 more·2021·Nature Metabolism

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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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.
Venue
Nature Metabolism
Published
2021-10-18
Volume
3
Issue
10
Pages
1327-1341
ISSN
2522-5812 (ISSN-L)
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
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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