Skeletal muscle mass, function, and repair capacity all progressively decline 
with aging, restricting mobility, voluntary function, and quality of life. 
Skeletal muscle repair is facilitated by a population of dedicated muscle stem 
cells (MuSCs), also known as satellite cells, that reside in anatomically 
defined niches within muscle tissues. In adult tissues, MuSCs are retained in a 
quiescent state until they are primed to regenerate damaged muscle through 
cycles of self-renewal divisions. With aging, muscle tissue homeostasis is 
progressively disrupted and the ability of MuSCs to repair injured muscle 
markedly declines. Until recently, this decline has been largely attributed to 
extrinsic age-related alterations in the microenvironment to which MuSCs are 
exposed. However, as highlighted in this Perspective, recent reports show that 
MuSCs also progressively undergo cell-intrinsic alterations that profoundly 
affect stem cell regenerative function with aging. A more comprehensive 
understanding of the interplay of stem cell-intrinsic and extrinsic factors will 
set the stage for improving cell therapies capable of restoring tissue 
homeostasis and enhancing muscle repair in the aged.