Muscle mitochondrial changes with aging and exercise.

Aging has been reported to be accompanied by reduced mitochondrial function and insulin sensitivity. Whether these deleterious effects result from chronological age or lifestyle-related factors such as adiposity and physical inactivity remains debatable. The beneficial effects of exercise on mitochondrial function and insulin sensitivity are well documented; however, it is unclear whether exercise can effectively prevent, reverse, or delay the onset of these age-related dysfunctions. Other investigators and we have found that endurance exercise enhances mitochondrial function across the life span, highlighting the beneficial role of exercise in combating age-related mitochondrial dysfunction. The literature is mixed concerning the ability of endurance exercise to normalize age-related insulin resistance; however, emerging evidence points to adiposity rather than age per se as a primary determinant of age-related declines in insulin sensitivity. Recent data from our laboratory also shed some light on the controversial relation between mitochondrial function and insulin sensitivity. Although some investigators purport a causal role of mitochondrial dysfunction in the etiology of insulin resistance, we provide evidence that the reverse may be true based on the fact that insulin stimulates mitochondrial function in healthy control subjects but not in patients with type 2 diabetes. Furthermore, we find that these 2 variables are completely dissociated in some populations, such as Asian Indians, who exhibit elevated mitochondrial capacity despite marked insulin resistance compared with European Americans. Our data not only point to regular endurance exercise as a viable strategy to delay the onset of age-related dysfunctions but they suggest that mitochondrial function and insulin resistance may be linked by additional factors such as physical activity.