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

• DOI: 10.1371/journal.pone.0063528
• Publication Date: 2013-05-21T17:11:40Z
• Authors: Wendy Cousin; Michelle Liane Ho; Rajiv Desai; Andrea Tham; Robert Yuzen Chen; Sunny Kung; Christian Elabd; Irina M. Conboy
• Keywords: Male; 0301 basic medicine; Aging; Skeletal Muscle; DNA Repair; Satellite Cells, Skeletal Muscle; General Science & Technology; 1.1 Normal biological development and functioning; Science; Medical Biotechnology; Medical Physiology; 612; Mice, SCID; Regenerative Medicine; Inbred C57BL; SCID; Muscle Development; Radiation Tolerance; Colony-Forming Units Assay; Double-Stranded; Mice; 03 medical and health sciences; Stem Cell Research - Nonembryonic - Human; Underpinning research; Genetics; Animals; Regeneration; DNA Breaks, Double-Stranded; Muscle, Skeletal; Cellular Senescence; Biomedical and Clinical Sciences; Stem Cells; DNA Breaks; Q; R; Skeletal; Stem Cell Research; Satellite Cells; Mice, Inbred C57BL; Musculoskeletal; Muscle; Medicine; Stem Cell Research - Nonembryonic - Non-Human; Generic health relevance; Research Article; DNA Damage

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.