Stem cells play a critical role in tissue repair and regeneration. However, as an organism ages, their function declines, leading to a reduction in tissue regeneration capacity and an increased risk of age-related diseases. Stem-cell exhaustion indicates stem cells and progenitor cells accruing damage over time, and eventually becoming depleted upon aging. Thus, aging is accompanied by a continuous decrease in tissue renewal, as well as with compromised tissue repair upon injury. This decline in stem cell function is due to a variety of factors, including increased cellular damage, changes in gene expression, and alterations in the microenvironment surrounding the stem cells. The suggested mechanisms of stem cell exhaustion include: