telomere shortening -DNA damage accumulated upon aging caused by a variety of factors, including oxidative stress, radiation, and chemical exposure epigenetic modifications, such as changes in DNA methylation or histone modifications, can alter gene expression and affect stem cell function. These changes can accumulate over time and contribute to stem cell exhaustion alterations in the stem cell microenvironment: the microenvironment, or niche, surrounding stem cells is critical for their function. Age-related changes in the niche, such as decreased nutrient and oxygen supply or the accumulation of toxic metabolites, can impair stem cell function. Studies have shown that stem cell exhaustion is a major contributing factor to age-related declines in tissue regeneration, including the loss of muscle mass, impaired bone healing, and decreased skin elasticity. Stem cell exhaustion also increases the risk of age-associated disorders such as Alzheimer's disease, cardiovascular disease, and cancer. Tissue repair is supposed to largely rely on injury-induced cellular de-differentiation and plasticity. Thus, in certain tissues, injury induces de-differentiation of multiple non-stem cells acquiring stem cell properties, attaining the plasticity necessary for tissue repair.