Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories

Highlights•The duration of eating/fasting varies based on diet type and feeding protocol•Meal feeding and CR, unlike AL, show high metabolic flexibility in male mice•Eating patterns rather than diet composition influence longevity regulation•A prolonged daily fasting is associated with delayed onset of liver pathologiesSummaryThe importance of dietary composition and feeding patterns in aging remains largely unexplored, but was implicated recently in two prominent nonhuman primate studies. Here, we directly compare in mice the two diets used in the primate studies focusing on three paradigms: ad libitum (AL), 30% calorie restriction (CR), and single-meal feeding (MF), which accounts for differences in energy density and caloric intake consumed by the AL mice. MF and CR regimes enhanced longevity regardless of diet composition, which alone had no significant impact within feeding regimens. Like CR animals, MF mice ate quickly, imposing periods of extended daily fasting on themselves that produced significant improvements in morbidity and mortality compared with AL. These health and survival benefits conferred by periods of extended daily fasting, independent of dietary composition, have major implications for human health and clinical applicability.Graphical abstract