Exercise-mediated modulation of autophagy in skeletal muscle

Abstract

Although exercise exerts multiple beneficial health effects, it may also damage cellular structures. Damaged elements are continuously degraded and its constituents recycled to produce renovated structures through a process called autophagy, which is essential for the adaptation to training. Autophagy is particularly active in skeletal muscle, where it can be evaluated using specific molecular markers of activation (unc-51-like kinase 1 [ULK1] phosphorylation) and specific proteins indicating increased autophagosome content (increased total LC3, LC3-II, LC3-II/LC3-I ratio). Studies in humans are technically limited but have provided evidence suggesting the activation of autophagy in skeletal muscle through AMP-activated protein kinase (AMPK) and its downstream target ULK1. Autophagy activation is more likely when the intensity is elevated and the exercise performed in the fasted state. The autophagy-gene program and autophagosome content are upregulated after ultraendurance running competitions. However, autophagosome content is reduced after endurance exercise at moderate intensities (50% and 70% of VO(2)max) for 60-120minutes. Autophagosome content is decreased within the first few hours after resistance training. The effects of regular endurance and strength training on basal autophagy remain to be established in humans. One study has reported that acute severe hypoxia increases autophagosome content in human skeletal muscle, which is reverted by 20minutes of low-intensity exercise. Experiments with transgenic mice have shown that autophagy is necessary for skeletal muscle adaptation to training. Little is known on how genetic factors, environment, nutrition, drugs and diseases may interact with exercise to modulate autophagy at rest and during exercise in humans.