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Intermittent and periodic fasting, longevity and disease

Abstract

Intermittent and periodic fasting (IF and PF, respectively) are emerging as safe strategies to affect longevity and healthspan by acting on cellular aging and disease risk factors, while causing no or minor side effects. IF lasting from 12 to 48 hours and repeated every 1 to 7 days and PF lasting 2 to 7 days and repeated once per month or less have the potential to prevent and treat disease, but their effect on cellular aging and the molecular mechanisms involved are only beginning to be unraveled. Here, we describe the different fasting methods and their effect on longevity in organisms ranging from yeast to humans, linking them to the major nutrient-sensing signaling pathways and focusing on the benefits of the fasting and the refeeding periods. We also discuss both the therapeutic potential and side effects of IF and PF with a focus on cancer, autoimmunity, neurodegeneration and metabolic and cardiovascular disease.

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Fig. 1: Fasting, nutrient signaling and longevity in yeast.
Fig. 2: Conserved nutrient-sensing response pathways in worms, flies and mammals.
Fig. 3: Periodic fasting and tissue regeneration and rejuvenation in mice.

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Acknowledgements

We would like to thank for their support the Associazione Italiana per la Ricerca sul Cancro (AIRC, IG nos. 17605 and 21820 to V.D.L.), the BC161452 grant of the Breast Cancer Research Program (US Department of Defense; to V.D.L.), and the NIA/NIH grants AG034906 and AG20642 to V.D.L.

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Correspondence to Valter D. Longo.

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V.D.L. declares the following competing interests: V.D.L. has equity interest in L-Nutra, a company that develops medical food. The University of Southern California has licensed intellectual property to L-Nutra. As part of this license agreement, the University has the potential to receive royalty payments from L-Nutra.

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Peer review information Nature Aging thanks Rozalyn Anderson, Stephen Simpson and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Longo, V.D., Di Tano, M., Mattson, M.P. et al. Intermittent and periodic fasting, longevity and disease. Nat Aging 1, 47–59 (2021). https://doi.org/10.1038/s43587-020-00013-3

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