Healthy skeletal muscle aging: The role of satellite cells, somatic mutations and exercise

Satellite cells (SCs) form the resident stem cell population in the skeletal muscle tissue. While their function in mediating tissue regeneration after injury is well described, their role in the undamaged-, aging-, and exercising muscle is only starting to be unraveled. Although direct evidence linking the loss of SC function to the onset of age-related loss of muscle mass and function (i.e., sarcopenia) is currently lacking, satellite cells are increasingly seen as an important component for the decline of tissue function seen with aging. This is evident from the pertinent role of SCs in maintaining homeostasis, and in mediating remodeling- and repair-responses, in the skeletal muscle. This narrative review focuses on human studies, but includes cellular and animal models, to describe the role of SCs in different physiological scenarios relevant for human aging. The intrinsic and extrinsic mechanisms underlying age-induced alterations in the SC pool are discussed, with particular emphasis on the genomic modifications that accumulate in human SCs during a lifetime (i.e., somatic mutation-burden). Finally, the role of exercise as a potential countermeasure to age-induced SC alterations is explored in the different scenarios covered.