Decline of regenerative potential of old muscle stem cells: contribution to muscle aging.

Muscle stem cells (MuSCs) are required for life-long muscle regeneration. In general, aging has been linked to a decline in the numbers and the regenerative potential of MuSCs. Muscle regeneration depends on the proper functioning of MuSCs, which is itself dependent on intricate interactions with its niche components. Aging is associated with both cell-intrinsic and niche-mediated changes, which can be the result of transcriptional, posttranscriptional, or posttranslational alterations in MuSCs or in the components of their niche. The interplay between cell intrinsic alterations in MuSCs and changes in the stem cell niche environment during aging and its impact on the number and the function of MuSCs is an important emerging area of research. In this review, we discuss whether the decline in the regenerative potential of MuSCs with age is the cause or the consequence of aging skeletal muscle. Understanding the effect of aging on MuSCs and the individual components of their niche is critical to develop effective therapeutic approaches to diminish or reverse the age-related defects in muscle regeneration.