Role of satellite cells in muscle growth and maintenance of muscle mass.

Changes in muscle mass may result from changes in protein turnover, reflecting the balance between protein synthesis and protein degradation, and changes in cell turnover, reflecting the balance between myonuclear accretion and myonuclear loss. Myonuclear accretion, i.e. increase in the number of myonuclei within the muscle fibers, takes place via proliferation and fusion of satellite cells, myogenic stem cells associated to skeletal muscle fibers and involved in muscle regeneration. In developing muscle, satellite cells undergo extensive proliferation and most of them fuse with myofibers, thus contributing to the increase in myonuclei during early postnatal stages. A similar process is induced in adult skeletal muscle by functional overload and exercise. In contrast, satellite cells and myonuclei may undergo apoptosis during muscle atrophy, although it is debated whether myonuclear loss occurs in atrophying muscle. An increase in myofiber size can also occur by changes in protein turnover without satellite cell activation, e.g. in late phases of postnatal development or in some models of muscle hypertrophy. The relative role of protein turnover and cell turnover in muscle adaptation and in the establishment of functional muscle hypertrophy remains to be established. The identification of the signaling pathways mediating satellite cell activation may provide therapeutic targets for combating muscle wasting in a variety of pathological conditions, including cancer cachexia, renal and cardiac failure, neuromuscular diseases, as well as aging sarcopenia.