Senescence in Myoblasts; Role in Age‐Related Muscle Dysfunction

Loss of skeletal muscle mass and function are critical factors in the development of frailty although the mechanisms by which this loss occurs are poorly understood. The number of senescent cells increases with age in rodents (Krishnamurthy et al ., 2004) and primates (Kreiling et al ., 2011) and it is proposed that the presence of these cells plays a role in age‐related muscle dysfunction. We hypothesise that resident satellite cells become senescent and exert detrimental effects on mature muscle fibres via the senescence associated secretory phenotype molecules (SASP). Initial studies have investigated whether a C2C12 mouse muscle myoblast cell line could be induced into senescence, whether key senescence associated molecules (such as p16, p21, and p53) are upregulated and determined the nature of the SASP. C2C12 myoblasts were treated for 24 hours with the topoisomerase II inhibitor, Etoposide, to cause DNA damage. Myoblasts were examined for up to 5 days following treatment for cell viability, Senescence Associated β‐Galactosidase (SAβ‐Gal) activity, immunocytochemistry and western blot analysis for p16, p21, and p53. Treated myoblasts exhibited a significantly altered morphology consistent with a senescence phenotype, increased SAβ‐Gal activity, and cyclin‐dependent kinase inhibitor levels compared with untreated cells. These data suggest that myoblasts can be induced into a senescent phenotype. Further work will characterise the SASP of the cells and determine the effect on mature myotubes co‐cultured with senescent myoblasts. Support or Funding Information Work generously funded by the British Society for Research into Ageing and the Rosetrees Trust. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .