Why do the regenerative capacities of stem cells diminish with age, and what can be done about it? This paper looks at some of the specific mechanisms as they work to suppress young transplanted cells: "aged differentiated [stem cell] niches dominantly inhibit [certain important gene expression] in activated satellite cells, and reduce proliferation and myogenic differentiation of both embryonic [hESCs] and tissue-specific adult stem cells (ASCs). ... the ability of hESCs, and the more differentiated myogenic ASCs to contribute to tissue repair in the old will be greatly restricted due to the conserved inhibitory influence of aged differentiated niches. ... hESC-derived factors enhance the regenerative potential of both young and, importantly, aged muscle stem cells in vitro and in vivo; thus, suggesting that the regenerative outcome of stem cell-based replacement therapies will be determined by a balance between negative influences of aged tissues on transplanted cells and positive effects of embryonic cells on the endogenous regenerative capacity. Comprehensively, this work points toward novel venues for in situ restoration of tissue repair in the old and identifies critical determinants of successful cell-replacement therapies for aged degenerating organs."