Abstract P649: Juvenile Exercise Delays Frailty and Promotes Metabolic Health in Aged Mice

Introduction: Physical exercise is well-recognized for its beneficial effects on health. Acute or short-term effects of exercise have been extensively studied; however, it remains unclear whether exercise in juvenile has sustained beneficial effects until old age. Hypothesis: We hypothesized that juvenile exercise would delay frailty and promote metabolic health in aged mice. Methods: Male and female mice were divided into sedentary and exercise groups, and each group contains 50 mice. Mice in exercise group started swimming at 1 month of age and stopped at 4 month of age (1.5 hour per day and 5 days per week). No exercise intervention was conducted in other time. The general health, cardiac function, metabolism and other parameters were examined in aged mice. Transcriptional profiling of various tissues and organs was performed to obtain insight into mechanisms that how juvenile exercise affects aged mice. Results: Juvenile exercise mice showed significant reduction in frailty and improvement in metabolic health compared with sedentary controls. Both male and female juvenile exercise mice were scored lower in frailty at the age of 24 months. Juvenile exercise improved the integument and physical/musculoskeletal status of male mice. For females, juvenile exercise reduced frailty in all aspects. Female juvenile exercise mice weighted more than sedentary mice at 24 months old but male groups showed no difference. The cardiac function, food consumption, grip strength and rotarod running time between two groups also presented no difference at 24 months. Juvenile exercise mice showed improved flexibility in substrate usage at the age of 24 months under fasting condition. Aged mice in exercise group showed significant higher energy expenditure, fat and carbohydrate oxidation than their controls. KEGG overrepresentation analysis for the differentially expressed genes demonstrated that pathways altered by juvenile exercise were most related to metabolism, especially lipid metabolism. Conclusions: These results demonstrate that regular and moderate physical exercise in juvenile age extends health span in mice, highlighting the sustained beneficial effects of juvenile exercise.