Editors' ChoicePhysiology

Periodic dieting promotes health

Sci. Signal.  14 Jul 2015:
Vol. 8, Issue 385, pp. ec187
DOI: 10.1126/scisignal.aac9913

Caloric restriction and fasting slow aging and extend life span in many species. In humans and rodents, intermittent fasting protects against metabolic and age-related diseases by, for example, improving insulin sensitivity and reducing blood pressure and inflammation. Brandhorst et al. found that switching yeast cells back and forth between nutrient-rich medium and water every two days greatly improved survival in the presence of hydrogen peroxide and extended the life span of the cells in a manner that was independent of conserved stress signaling components previously implicated in longevity. To investigate the effects of periodic fasting in mice, the authors developed a low-calorie, low-protein fasting-mimicking diet (FMD) that caused changes in metabolic markers [blood glucose, ketone bodies, insulin, insulin-like growth factor 1 (IGF-1), and the IGF-1 inhibitor IGFBP-1] that were similar to those induced by fasting and were reversed by resumption of ad libitum feeding. For several months, aged mice received the FMD for four days twice per month, with an ad libitum diet of normal chow in between FMD cycles. The FMD mice increased their food consumption between FMD cycles, resulting in no net difference in cumulative calorie intake compared to control mice, yet the mice subjected to FMD cycles gradually lost weight. FMD cycling had no detectable effect on cardiac or kidney function, and refeeding induced liver and skeletal muscle regeneration. Compared with control mice, aged mice subjected to FMD cycling had fewer spontaneous tumors, greater bone density, more hippocampal neurogenesis, increased tissue-protective autophagy in skeletal muscle, and reduced visceral fat mass, inflammation, and immunosenescence. FMD cycling also increased life span and improved performance in tests of motor coordination, working memory, and long-term memory. A group of healthy human volunteers were randomly split into a control group that made no changes to their normal diet and group that consumed an FMD, which delivered all essential micronutrients and between 725 and 1000 calories per day, for five consecutive days per month for three months with no changes to their normal exercise routines or eating habits in between FMD cycles. After resuming their normal diets at the end of three months, the FMD group had increased lean body mass and sustained reductions in blood glucose, circulating IGF-1, body weight, abdominal fat, and C-reactive protein, a risk factor for heart disease. Although further longer-term human studies are necessary to more thoroughly characterize the effects of periodic fasting on metabolism, aging, and longevity, these results offer tantalizing evidence that periodic regular consumption of a balanced low-calorie diet may have many health benefits.

S. Brandhorst, I. Y. Choi, M. Wei, C. W. Cheng, S. Sedrakyan, G. Navarrete, L. Dubeau, L. P. Yap, R. Park, M. Vinciguerra, S. Di Biase, H. Mirzaei, M. G. Mirisola, P. Childress, L. Ji, S. Groshen, F. Penna, P. Odetti, L. Perin, P. S. Conti, Y. Ikeno, B. K. Kennedy, P. Cohen, T. E. Morgan, T. B. Dorff, V. D. Longo, A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metab. 22, 86–99 (2015). [PubMed]

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