Metabolic and physical function are improved with lifelong 15% calorie restriction in aging male mice.

Chronic calorie restriction (CR) results in lengthened lifespan and reduced disease risk. Many previous studies have implemented 30-40% calorie restriction to investigate these benefits. The goal of our study was to investigate the effects of calorie restriction, beginning at 4 months of age, on metabolic and physical changes induced by aging. Male C57BL/6NCrl calorie restricted and ad libitum fed control mice were obtained from the National Institute on Aging (NIA) and studied at 10, 18, 26, and 28 months of age to better understand the metabolic changes that occur in response to CR in middle age and advanced age. Food intake was measured in ad libitum fed controls to assess the true degree of CR (15%) in these mice. We found that 15% CR decreased body mass and liver triglyceride content, improved oral glucose clearance, and increased all limb grip strength in 10- and 18-month-old mice. Glucose clearance in ad libitum fed 26- and 28-month-old mice is enhanced relative to younger mice but was not further improved by CR. CR decreased basal insulin concentrations in all age groups and improved insulin sensitivity and rotarod time to fall in 28-month-old mice. The results of our study demonstrate that even a modest reduction (15%) in caloric intake may improve metabolic and physical health. Thus, moderate calorie restriction may be a dietary intervention to promote healthy aging with improved likelihood for adherence in human populations.