Stem cell depletion is one of the aging hallmarks. Age-associated impairments in stem cell functions correlate with a decline in somatic tissue regeneration seen in aging (and under pathological conditions). Indeed, loss of stem cell functions is believed to contribute loss of tissue functions, which may lead to premature organismal death. The functional decline of aging stem cells is believed to be due to changes in the microenvironment that govern stem cell maintenance or cell fate. Excessive reactive oxygen species partly due to defects in energy metabolism have been linked to stem cell aging. In addition, the accumulation of DNA damage has been noted in aging stem cells. Furthermore, other reports demonstrated that aged stem cells divide more frequently in low turnover tissues due to the disruption of stem cell quiescence. The Cheung Laboratory is focused on utilizing a multi-omics approach to study stem cell aging, using satellite cells as a model of biological aging, as they spend much of their lifespan in quiescence. Indeed, aging skeletal muscle exhibits a decline in mass and function declines, resulting in a loss of muscle strength. Therefore, a better understanding of the cellular changes of satellite cells during the aging process will provide important insights into the design of novel therapeutic approaches based on enhancing stem cell functions.