Resident muscle stem cells (MuSCs) are essential for the regeneration of muscle. However, over time, there is a gradual depletion of the MuSC pool. While aged MuSCs display cell-autonomous deficits that contribute to impaired regeneration, a young microenvironment, or niche, can restore a youthful cellular phenotype. Most studies to date have focused on the effects of circulating factors on age-related functional decline of MuSCs, however, little is known about the effect of biophysical niche alterations on MuSC self-renewing potential. Studies from our laboratory have revealed that the matrix stiffness of an aged niche contributes to the loss of MuSC self-renewal. Importantly, self-renewal of aged MuSCs can be restored by exposing cells to matrices characteristic of young muscle. The findings of this project may be useful both for the maintenance of the stem cell pool with age, as well as therapeutic interventions to restore muscle health in the elderly population.