A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan

Brandhorst, Sebastian; Choi, In Young; Wei, Min; Cheng, Chia Wei; Sedrakyan, Sargis; Navarrete, Gerardo; Dubeau, Louis; Yap, Li Peng; Park, Ryan; Vinciguerra, Manlio; Di Biase, Stefano; Mirzaei, Hamed; Mirisola, Mario G.; Childress, Patra; Ji, Lingyun; Groshen, Susan; Penna, Fabio; Odetti, Patrizio; Perin, Laura; Conti, Peter S.; Ikeno, Yuji; Kennedy, Brian K.; Cohen, Pinchas; Morgan, Todd E.; Dorff, Tanya B.; Longo, Valter D.

doi:10.1016/j.cmet.2015.05.012

Cited by 850Dietary Effects on HealthGenetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in Medicine

A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan

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Brandhorst, Sebastian, Choi, In Young, Wei, Min, Cheng, Chia Wei, Sedrakyan, Sargis, Navarrete, Gerardo, Dubeau, Louis, Yap, Li Peng +18 more·2015·Cell Metabolism

DOI 10.1016/j.cmet.2015.05.012PMC PMC4509734

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Abstract

Prolonged fasting (PF) promotes stress resistance, but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. In mice, 4 days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems, an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss. In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease, and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan.

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Exercise and dietary changes including caloric restriction and intermittent fasting can slow and even reverse aging progression.
“Exercise and dietary changes, including caloric restriction and intermittent fasting, can slow and even reverse the progression of aging (Brandhorst et al., 2015; Fontana and Partridge, 2015; Garatachea et al., 2015; Mercken et al., 2012)”
From The Aging Epigenome (2016) · cites this paper as Brandhorst et al., 2015
In aged mice, the fasting-mimicking diet with cycles of fasting and refeeding enhances neurogenesis in the hippocampus.
“In aged mice, the fasting-mimicking diet with cycles of fasting and refeeding enhances neurogenesis in the hippocampus208.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [208]
The fasting-mimicking diet has a bona fide rejuvenation effect on multiple organs in mice.
“Among different regimens, the fasting-mimicking diet has been shown to have a bona fide rejuvenation effect on multiple organs in mice208, which may be due to alternating cycles of fasting and feeding.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [208]

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Authors: Brandhorst, S., Choi, I. Y., Wei, M., Cheng, C. W., Sedrakyan, S., Navarrete, G., Dubeau, L., Yap, L. P., Park, R., Vinciguerra, M., Di Biase, S., Mirzaei, H., Mirisola, M. G., Childress, P., Ji, L., Groshen, S., Penna, F., Odetti, P., Perin, L., Conti, P. S., Ikeno, Y., Kennedy, B. K., Cohen, P., Morgan, T. E., Dorff, T. B., & Longo, V. D.
Affiliations: University of Southern California (US)
The Royal Free Hospital (GB)
University of Palermo (IT)
University of Turin (IT)
University of Genoa (IT)
The University of Texas at San Antonio Health Science Center (US)
Buck Institute for Research on Aging (US)
Corresponding author: Longo, Valter D.
ORCID: Brandhorst, Sebastian
Choi, In Young
Wei, Min
Sedrakyan, Sargis
Dubeau, Louis
Vinciguerra, Manlio
Mirisola, Mario G.
Childress, Patra
Ji, Lingyun
Groshen, Susan
Penna, Fabio
Odetti, Patrizio
Perin, Laura
Conti, Peter S.
Ikeno, Yuji
Kennedy, Brian K.
Cohen, Pinchas
Morgan, Todd E.
Dorff, Tanya B.
Longo, Valter D.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2015-07
Volume: 22
Issue: 1
Pages: 86-99
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2015.05.012
PMC: PMC4509734
OpenAlex: W2168705381
Cited by: 850
References: 73
Citations by year: 2026: 55 · 2025: 76 · 2024: 84 · 2023: 113 · 2022: 87 · 2021: 99 · 2020: 98 · 2019: 61 · 2018: 61 · 2017: 55 · 2016: 45 · 2015: 15
FWCI: 43.19
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 372 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
UCL Discovery (University College London) (submittedVersion)
CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
Funders: National Institutes of Health (1s10rr017964-01)
National Institute on Aging (P01AG034906, AG20642, R01AG020642, AG034906, AG025135, R01AG025135, P30AG013319)
National Center for Research Resources (S10 RR017964, S10RR017964-01)
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: intermittent fasting, time-restricted feeding, healthspan, longevity, tissue regeneration, stem cells, progenitor cells, hippocampal neurogenesis, cognitive performance, insulin-like growth factor I, PKA signaling, NeuroD1, immune rejuvenation, bone mineral density, visceral fat, cancer incidence, aging biomarkers
MeSH terms: Adult, Aged, Aging, Animals, Body Weight, Cardiovascular Diseases, Cognition, Diet, Fasting, Female, Humans, Longevity, Male, Mice, Inbred C57BL, Middle Aged, Neoplasms, Pilot Projects, Psychomotor Performance, Regeneration, Saccharomyces cerevisiae, Abdominal Fat, Mice, Neurogenesis, Young Adult

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A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan

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