Defect of autophagy signaling in sarcopenic muscle

Abstract Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Autophagy occurs in all eukaryotic cells and is evolutionarily conserved from yeast to human beings. The autophagy machinery is a critical pathway for cell homeostasis, but it has been insufficiently studied in skeletal muscle. Particular emphasis has been given on the role played by autophagic defects in disease pathogenesis, its involvement in atrophy, and the possible effects of exercise as a countermeasure. Recent studies indicated that the age-related defects of autophagy signaling in normal skeletal muscle, whereas denervation, unloading, and cachexia, frequently involved with aging, modulate the autophagy-dependent system. The autophagic defect in sarcopenia may be influenced by new candidates [glycogen synthase kinase (GSK)-3a, mitofusin 2, and Rubicon]. Endurance training and calorie restriction have positive effects on sarcopenia and several forms of muscle wasting by activating the autophagy system. This review describes recent research advances regarding autophagy-dependent signaling in sarcopenia.