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Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012. Epub 2015 Jun 18.

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

Author information

1
Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
2
GOFARR Laboratory, Children's Hospital Los Angeles, Division of Urology, Saban Research Institute, University of Southern California, Los Angeles, CA 90089, USA.
3
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
4
Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
5
Institute for Liver and Digestive Health, Division of Medicine, University College London, Royal Free Hospital, London NW3 2PF, UK.
6
Department of Pathobiology and Medical Biotechnology, University of Palermo, 90100 Palermo, Italy.
7
Global Medicine Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
8
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
9
Department of Clinical and Biological Sciences, University of Torino, 10100 Torino, Italy.
10
Department of Internal Medicine, University of Genova, 16146 Genova, Italy.
11
Department of Pathology, Barshop Institute, University of Texas Health Science Center, San Antonio, TX 78229, USA.
12
Buck Institute for Research on Aging, Novato, CA 94945, USA.
13
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
14
Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA; IFOM, FIRC Institute of Molecular Oncology, 20139 Milano, Italy. Electronic address: vlongo@usc.edu.

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.

PMID:
26094889
PMCID:
PMC4509734
DOI:
10.1016/j.cmet.2015.05.012
[Indexed for MEDLINE]
Free PMC Article

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