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

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, four 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.

Circadian clocks: from stem cells to tissue homeostasis and regeneration

“…Another two recent studies show that epidermal as well as skeletal muscle stem cells retain robust circadian rhythms upon aging, but that the set of oscillatory output gene changes from genes involved in homeostasis to tissue‐specific stress‐associated genes involved in DNA damage and inefficient autophagy 73, 74. The authors could prevent age‐associated rewiring of the circadian transcriptome by long‐term caloric restriction in aged mice, which is line with an earlier found correlation between low‐fat diet and reduced aging 73, 75. This means that stem cells can adapt their circadian transcriptome to different conditions of metabolic states and organ‐specific stresses.…”

Beyond Computational Genomics towards Systems Metabolomics for Precision Oncology

“…Metabolic rewirings are hypothesized to underlay aging (78), metabolic syndrome (79), nutrition and wellness (80). The construction of the corresponding models and the discovery of their design principles will substantially advance our understanding in these challenging areas.…”

Slowing Polycystic Kidney Disease by Fasting

“…14 While awaiting for the miraculous pill, an exciting study recently described the beneficial effects of a new diet mimicking intermittent fasting. 15 Brandhorst et al 15 showed that, in yeast, cycles of fasting followed by refeeding can also extend lifespan. Furthermore, the bimonthly administration of a diet that mimics the effects of intermittent fasting extended the median lifespan of mice (not their absolute lifespan), reduced cancer incidence, and rejuvenated the immune system.…”

“…Furthermore, the bimonthly administration of a diet that mimics the effects of intermittent fasting extended the median lifespan of mice (not their absolute lifespan), reduced cancer incidence, and rejuvenated the immune system. Importantly, Brandhorst et al 15 also performed a small randomized pilot clinical trial and showed that a fast-mimicking diet recapitulated, at least in part, the effect of intermittent fasting for several parameters in humans as well. Thus, diets ensuring intermittent calorie restriction might ultimately provide a reasonable therapy for a number of diseases, including ADPKD.…”