Effects of low-dose γ-radiation on skeletal muscle stem cells

Introduction: Exposure to low dose ionizing radiation (LDIR) has been associated with aging related health effects. The aging related decline in the regenerative capacity of muscle stem cells in elderly individuals, as well as other myopathy conditions, represents a major health issue. Effects of LDIR exposures, such as those from routine medical CT scans on functional status of muscle stem cells, are not known.Methods: We investigated how a single acute 60Co γ-irradiation (10 and 100 mGy) affected myogenesis into mature muscle fibers in cultures of mouse C2C12 myoblasts and biopsy-derived human skeletal muscle stem cells.Results: We observed a substantial decrease in differentiation capacity in unirradiated control cells with age and time in culture; the loss of differentiation potential was partially restored in cultures exposed to LDIR at early passage. In C2C12 cells, LDIR exposure also resulted in lower frequencies of cells with anaphase bridges and micronuclei throughout the aging in vitro experiment, suggesting a suppressed genomic instability state. In human cells, mutational burden readouts assessed by the TruSight Oncology 500 NGS-based assay revealed no changes in LDIR-exposed cells vs. non-irradiated controls.Conclusion: Our results propose that exposure to single acute dose of LDIR lead to a partial reversal of an aging-related decline of the myogenic function in muscle myoblasts. In human cells, this effect was concurrent with the lack of accumulation of a mutational burden, while in mouse cells the results suggest improved genome integrity.