title: A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan.
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.
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandhorst
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: In Young
authors.initials: IY
authors.lastname: Choi
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Chia Wei
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: GOFARR Laboratory, Children's Hospital Los Angeles, Division of Urology, Saban Research Institute, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Sargis
authors.initials: S
authors.lastname: Sedrakyan
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Navarrete
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Dubeau
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Li Peng
authors.initials: LP
authors.lastname: Yap
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Park
authors.affiliation: Institute for Liver and Digestive Health, Division of Medicine, University College London, Royal Free Hospital, London NW3 2PF, UK.
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Biase
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Hamed
authors.initials: H
authors.lastname: Mirzaei
authors.affiliation: Department of Pathobiology and Medical Biotechnology, University of Palermo, 90100 Palermo, Italy.
authors.forename: Mario G
authors.initials: MG
authors.lastname: Mirisola
authors.affiliation: Global Medicine Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Patra
authors.initials: P
authors.lastname: Childress
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, 10100 Torino, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Penna
authors.affiliation: Department of Internal Medicine, University of Genova, 16146 Genova, Italy.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Odetti
authors.affiliation: GOFARR Laboratory, Children's Hospital Los Angeles, Division of Urology, Saban Research Institute, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Perin
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
authors.affiliation: Department of Pathology, Barshop Institute, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeno
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kennedy
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.affiliation: Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Tanya B
authors.initials: TB
authors.lastname: Dorff
authors.affiliation: 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.
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D050153:Abdominal Fat / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging; D000818:Animals; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000178:diet therapy / Q000378:metabolism; D003071:Cognition; D004032:Diet; D005215:Fasting; D005260:Female; D006801:Humans; D008136:Longevity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009369:Neoplasms / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis; D010865:Pilot Projects; D011597:Psychomotor Performance; D012038:Regeneration; D012441:Saccharomyces cerevisiae / Q000166:cytology; D055815:Young Adult