A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan

Sebastian Brandhorst, In Young Choi, Min Wei, Chia Wei Cheng, Sargis Sedrakyan, Gerardo Navarrete, Louis Dubeau, Li Peng Yap, Ryan Park, Manlio Vinciguerra, Stefano Di Biase, Hamed Mirzaei, Mario G. Mirisola, Patra Childress, Lingyun Ji, Susan Groshen, Fabio Penna, Patrizio Odetti, Laura Perin, Peter S. Conti & 6 others Yuji Ikeno, Brian K. Kennedy, Pinchas Cohen, Todd E. Morgan, Tanya B. Dorff, Valter D. Longo

Research output: Contribution to journalArticle

191 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)86-99
Number of pages14
JournalCell Metabolism
Volume22
Issue number1
DOIs
StatePublished - Jul 7 2015

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Regeneration
Fasting
Diet
Stem Cells
Organ Size
Intra-Abdominal Fat
Neurogenesis
Skin Neoplasms
Insulin-Like Growth Factor I
Bone Density
Immune System
Cardiovascular Diseases
Yeasts
Biomarkers
Clinical Trials
Food
Incidence
Genes
Neoplasms

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Brandhorst, S., Choi, I. Y., Wei, M., Cheng, C. W., Sedrakyan, S., Navarrete, G., ... Longo, V. D. (2015). A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metabolism, 22(1), 86-99. https://doi.org/10.1016/j.cmet.2015.05.012

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.

In: Cell Metabolism, Vol. 22, No. 1, 07.07.2015, p. 86-99.

Research output: Contribution to journalArticle

Brandhorst, S, Choi, IY, Wei, M, Cheng, CW, Sedrakyan, S, Navarrete, G, Dubeau, L, Yap, LP, Park, R, Vinciguerra, M, Di Biase, S, Mirzaei, H, Mirisola, MG, Childress, P, Ji, L, Groshen, S, Penna, F, Odetti, P, Perin, L, Conti, PS, Ikeno, Y, Kennedy, BK, Cohen, P, Morgan, TE, Dorff, TB & Longo, VD 2015, 'A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan', Cell Metabolism, vol. 22, no. 1, pp. 86-99. https://doi.org/10.1016/j.cmet.2015.05.012
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. / A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. In: Cell Metabolism. 2015 ; Vol. 22, No. 1. pp. 86-99.
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