The altered fate of aging satellite cells is determined by signaling and epigenetic changes

Skeletal muscle is a striated tissue composed of multinucleated fibers that contract under the control of the somatic nervous system to direct movement. The stem cells of skeletal muscle, known as satellite cells, are responsible for muscle fiber growth, turnover, and regeneration. Satellite cells are activated and proliferate in response to stimuli, and simplistically, have two main fates—to repopulate the satellite cell niche, or differentiate to regenerate or repair muscle fibers. However, the ability to regenerate muscle and replace lost myofibers declines with age. This loss of function may be a result of extrinsic changes in the niche, such as alterations in signaling or modifications to the extracellular matrix. However, intrinsic epigenetic changes within satellite cells may also affect cell fate and cause a decline in regenerative capacity. This review will describe the mechanisms that regulate cell fate decisions in adult skeletal muscle, and how changes during aging affect muscle fiber turnover and regeneration.