Abstract 4141191: Early-life Exercise Extends Healthspan and Attenuates Cardiovascular Aging in Aged Mice

Introduction: Regular physical exercise is widely recognized for its beneficial effects on overall health. Despite emerging evidence that early-life experiences profoundly impact adult and aged health, the long-term effects of early-life exercise remain uncertain. Hypothesis: We hypothesized that early-life exercise extends healthspan and attenuates cardiovascular aging in aged mice. Methods: Male and female C57BL/6J mice were subjected to a 3-month swimming exercise regimen starting from 1 month of age (1.5 hour per day, 5 days per week), while no exercise intervention was conducted at other times. The sedentary group was raised under similar conditions. The healthspan of aged male and female mice was assessed, including overall metabolic function, cardiovascular function, frailty index and other relevant measurements. Transcriptional profiling of young and old mice was performed to gain insights into the mechanisms underlying the effects of early-life exercise on aging. Results: Early-life exercise improved metabolic health in aged mice. Assessment of body composition showed increased lean mass in the exercise group. When subjected to food deprivation stress in metabolic chambers, aged mice with early-life exercise exhibited increased energy expenditure, carbohydrate oxidation, and fat oxidation levels in both males and females. Evaluation of frailty index at 24 months of age, involving 31 frailty phenotypes, indicated lower frailty index score in the early-life exercise group, suggesting an attenuation of age-related phenotypes. While no significant differences were observed in blood pressure and cardiac systolic function, early-life exercise was associated with improved cardiac diastolic function at 19 months of age. Furthermore, early-life exercise resulted in decreased heart-carotid pulse wave velocity and improved endothelial-dependent vascular relaxation in aged mice, indicating better vascular function in elderly mice with early-life exercise. Conclusions: The findings demonstrate that early-life exercise contributes to an increased healthspan, as evidenced by enhanced metabolic health and reduced frailty. Both male and female aged mice exposed to early-life exercise exhibit improved cardiovascular function.