Do senescent cells drive the ageing phenotype of skeletal muscle in vivo?

Loss of skeletal muscle mass and function are critical factors in the development of frailty. The number of senescent cells increases with age in rodents (Krishnamurthy et al., 2004) and primates (Kreiling et al., 2011). We hypothesise that these cells trigger a local and/or systemic chronic inflammatory status in old mice with the production of senescence associated secretory phenotype molecules (SASPs) and we further hypothesise that this leads to the activation of NF‐kB mediated inflammatory pathway seen in skeletal muscle of old mice (Vasilaki et al, 2006), potentially by the so‐called bystander effect (Nelson et al, 2017). Initial studies have investigated whether key senescence associated molecules (such as p16, p21, and p53) are increased in the muscle bulk of old (24 months old) compared with young (3 months old) C57BL6 Wild Type (WT) mice in vivo. Whole quadriceps muscles from young and old mice were subjected to western blot analysis for senescence associated cyclin‐dependent kinase inhibitors, including p16, p21 and p53. Western blot analysis demonstrated that muscle from old mice showed a significantly increased content of p16, p21, and p53 compared with muscles of young mice (p<0.05) and analyses are underway to characterise the nature of cells expressing these senescent proteins within the muscle bulk. Further studies will determine the potential production of a SASP by these cells and the effect on chronic activation of NF‐kB in muscle fibres of old mice. 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 .