Regeneration of skeletal muscle relies on a population of quiescent stem cells (satellite cells) and is impaired in very old (geriatric) individuals undergoing sarcopenia. Stem cell function is essential for organismal homeostasis, providing a renewable source of cells to repair damaged tissues. In adult organisms, age-dependent loss-of-function of tissue-specific stem cells is causally related with a decline in regenerative potential. Although environmental manipulations have shown good promise in the reversal of these conditions, recently we demonstrated that muscle stem cell aging is, in fact, a progressive process that results in persistent and irreversible changes in stem cell intrinsic properties. Global gene expression analyses uncovered an induction of p16^INK4a in satellite cells of physiologically aged geriatric and progeric mice that inhibits satellite cell-dependent muscle regeneration. Aged satellite cells lose the repression of the INK4a locus, which switches stem cell reversible quiescence into a pre-senescent state; upon regenerative or proliferative pressure, these cells undergo accelerated senescence (geroconversion), through Rb-mediated repression of E2F target genes. p16^INK4a silencing rejuvenated satellite cells, restoring regeneration in geriatric and progeric muscles. Thus, p16^INK4a/Rb-driven stem cell senescence is causally implicated in the intrinsic defective regeneration of sarcopenic muscle. Here we discuss on how cellular senescence may be a common mechanism of stem cell aging at the organism level and show that induction of p16^INK4a in young muscle stem cells through deletion of the Polycomb complex protein Bmi1 recapitulates the geriatric phenotype.