Voluntary Exercise-Induced Skeletal Muscle Responses in Young and Aged Mice on a High-Fat Diet.

Background and objective Aging and consumption of a high-fat diet (HFD) are associated with increased body weight and reduced skeletal muscle quality. Although aerobic exercise is generally considered protective against these risks, the impact of self-initiated physical activity on an HFD in older individuals remains unclear. This study aimed to investigate the influence of spontaneous wheel-running on body weight, intramuscular fat accumulation, and mitochondrial metabolic function in the skeletal muscles of young and aged mice on HFD. Methods Male C57BL/6J mice aged 14 weeks (young group) and 84 weeks (aged group) were assigned to either exercise or sedentary groups and fed an HFD for eight weeks. Measurements included body weight, muscle weight (gastrocnemius and soleus), muscle fiber cross-sectional area (FCSA), succinate dehydrogenase (SDH) activity, and intramuscular fat area via Oil Red O staining. Results Voluntary exercise significantly reduced the body weight in both age groups. While the muscle weight and FCSA remained unchanged by exercise, exercise led to elevated SDH activity in the gastrocnemius muscles of both young and aged mice, suggesting increased mitochondrial metabolic activity. Exercise increased intramuscular fat content in the gastrocnemius muscle of young mice, but not in aged mice. The soleus muscle showed a minimal response to both metabolic activity and fat accumulation by exercise, regardless of age. Conclusions Voluntary wheel running under HFD conditions effectively lowered body weight and increased mitochondrial activity in gastrocnemius muscle fibers. However, intramuscular fat responses vary according to muscle type and age, suggesting that aging diminishes skeletal muscle adaptability to exercise in the context of lipid metabolism.