The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.
Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice
Open accessAbstract
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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“Intermittent fasting (e.g., one day without nutrients, followed by one day of ad libitum feeding) can avoid long-term weight loss induced by caloric restriction, yet increases lifespan in mice 148 and improves biomarkers of health in clinical trials 153,154 .”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [148]
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“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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Cites
Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Allison, D. B., Cruzen, C., Simmons, H. A., Kemnitz, J. W., et al. (2009) · Science · doi:10.1126/science.1173635 · Cited by 2,277
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The underappreciated role of muscle in health and disease
Wolfe, R. R. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.3.475 · Cited by 1,629
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Fasting: molecular mechanisms and clinical applications
Longo, V. D., & Mattson, M. P. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.008 · Cited by 1,425
Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study
Mattison, J. A., Roth, G. S., Beasley, T. M., Tilmont, E. M., Handy, A. M., Herbert, R. L., Longo, D. L., Allison, D. B., Young, J. E., Bryant, M., et al. (2012) · Nature · doi:10.1038/nature11432 · Cited by 1,145
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NetworkAnalyst for statistical, visual and network-based meta-analysis of gene expression data
Xia, J., Gill, E. E., & Hancock, R. E. W. (2015) · Nature Protocols · doi:10.1038/nprot.2015.052 · Cited by 954
Wilkinson, M. J., Manoogian, E. N. C., Zadourian, A., Lo, H., Fakhouri, S., Shoghi, A., Wang, X., Fleischer, J. G., Navlakha, S., Panda, S., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.004 · Cited by 927
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Hallmarks of aging: An expanding universe
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023) · Cell · doi:10.1016/j.cell.2022.11.001 · Cited by 6,549
Molecular mechanisms of dietary restriction promoting health and longevity
Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714
Self-citationCircadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice
Acosta-Rodríguez, V., Rijo-Ferreira, F., Izumo, M., Xu, P., Wight-Carter, M., Green, C. B., & Takahashi, J. S. (2022) · Science · doi:10.1126/science.abk0297 · Cited by 390
Self-citationDietary restriction impacts health and lifespan of genetically diverse mice
Francesco, A. D., Deighan, A. G., Litichevskiy, L., Chen, Z., Luciano, A., Robinson, L. L., Garland, G., Donato, H., Vincent, M. J., Schott, W., et al. (2024) · Nature · doi:10.1038/s41586-024-08026-3 · Cited by 204
Regulators of health and lifespan extension in genetically diverse mice on dietary restriction
Di Francesco, A., Deighan, A. G., Litichevskiy, L., Chen, Z., Luciano, A., Robinson, L., Garland, G., Donato, H., Schott, W., Wright, K. M., et al. (2023) · doi:10.1101/2023.11.28.568901 · Cited by 194
Metadata
- 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 (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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