Mitophagy Regulation in Skeletal Muscle: Effect of Endurance Exercise and Age

Abstract

Mitochondria are essential energy-providing organelles that are required in the maintenance of healthy skeletal muscle. As such, the removal of damaged mitochondria, through mitophagy, is necessary to maintain mitochondrial quality. In aging muscle, mitochondrial content and function are often found to be reduced compared to young individuals. This occurs despite the fact that measures of mitophagy are elevated, suggesting that mitophagy is insufficiently high to remove all of the dysfunctional organelles in aging muscle. Recent evidence has shown that acute exercise promotes mitophagic signaling, leading to organelle degradation. This exercise-induced signaling is attenuated in aging muscle, suggesting that aging muscle loses its capacity for mitochondrial turnover in response to exercise. This contributes to the reduction in muscle health in elderly individuals. Chronic exercise training improves mitochondrial content and function, even in aging muscle, leading to reduced mitophagy signaling. Thus, exercise training should be prescribed for both young and elderly populations to promote the maintenance of a healthy mitochondrial pool, through the stimulation of both organelle biogenesis and mitophagy.

Mitophagy in Human Diseases

“…Moreover, mitochondria also differ between red muscles rich in type I fibers with densely interconnected mitochondria and fast twitching white muscles bearing mainly type II fibers with lower mitochondrial content, which are more prone to wasting. Both aging and physical training greatly modify mitochondria turnover and efficiency in this context [ 383 , 384 ]. The capacity to adapt mitochondrial activity to energetic requirements and exercise levels characterizes skeletal muscles in the young and is gradually lost during aging despite increased mitophagy fluxes in the old [ 385 ].…”

Impact of Melatonin on Skeletal Muscle and Exercise

“…This connection is particularly evident in differences between endurance or power muscles in athletes influencing sports performance, degree of vascularization, and mitochondria1 function [132]. A great deal of evidence indicates that mitophagy in muscle is activated by exercise but is abnormal in aging if mitophagy flux is excessive and mitochondrial quality reduced [133,134]. Multiple receptors and signals are involved to drive proper mitochondria turnover in skeletal muscle and to regulate lysosomal homeostasis.…”