Impact of Aging and Lifelong Exercise Training on Mitochondrial Function and Network Connectivity in Human Skeletal Muscle.

Aging is associated with metabolic decline and reduction in mitochondrial function in skeletal muscle which can be delayed by physical activity. Moreover, exercise training has been shown to prevent age-associated decline in mitochondrial function and fragmentation of the mitochondrial network in mouse skeletal muscle. However, whether lifelong endurance exercise training exerts the same effects in human skeletal muscle is still not clear. Therefore, the aim of the present study was to examine the effect of volume-dependent lifelong endurance exercise training on mitochondrial function and network connectivity in older human skeletal muscle. Skeletal muscle complex I+II-linked mitochondrial respiration per tissue mass was higher, but intrinsic complex I+II-linked mitochondrial respiration was lower in highly trained older than in young untrained, older untrained and older moderately trained men. Mitochondrial volume and connectivity were higher in highly trained older than in untrained and moderately trained older subjects. Furthermore, protein content of the ADP/ATP exchangers ANT1 + 2 and VDAC was higher and of the mitophagic marker Parkin lower in skeletal muscle from the highly trained older than from untrained and moderately trained older subjects. In contrast, H2O2 emission in skeletal muscle was not affected by either age or exercise training, but SOD2 protein content was higher in highly trained older than in untrained and moderately trained older subjects. This suggests that healthy aging does not induce oxidative stress or mitochondrial network fragmentation in human skeletal muscle, but high-volume exercise training increases mitochondrial volume and network connectivity, thereby increasing oxidative capacity in older human skeletal muscle.