Regenerative Capacity of Old Muscle Stem Cells Declines without Significant Accumulation of DNA Damage

摘要: The performance of adult stem cells is crucial for tissue homeostasis but their regenerative capacity declines with age, leading to failure multiple organs. In skeletal muscle this manifested by the loss functional tissue, accumulation fibrosis, and reduced satellite cell-mediated myogenesis in response injury. While recent studies have shown that changes composition cell niche are at least part responsible impaired function observed aging, little known about effects aging on intrinsic properties cells. For instance, ability repair DNA damage a potential double strand breaks (DSBs) remain unclear. This work demonstrates old display no significant DSBs when compared those young, as assayed after isolation sections, either uninjured or time points Additionally, there difference expression DSB proteins globally genes, suggesting not only DSBs, also other types damage, do significantly mark aged Satellite from DSB-repair-deficient SCID mice an unsurprisingly higher level innate weakened recovery gamma-radiation-induced damage. Interestingly, they myogenic vitro vivo young wild type mice, inefficiency does directly correlate regenerate Overall, our findings suggest DSB-repair deficiency unlikely be key factor decline regeneration upon aging.