CHARACTERISATION OF NF‐KB ACTIVATION IN REGENERATING FIBRES OF OLD MICE

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Sarcopenia is the age‐related loss of muscle mass and function. In human studies a decrease of up to 50% in muscle mass and function is observed from the ages of 25 to 70 years and this contributes significantly to frailty and loss of independence in the ageing population. An increase in pro‐inflammatory cytokines is associated with many age‐related conditions including sarcopenia (particularly TNF‐alpha and IL‐6). Many inflammatory processes are under the direct influence of the NF‐κB pathway and a chronic activation of NF‐κB has been shown in muscles from old mice and in accelerated models of muscle ageing (eg. Vasilaki et al, 2006). Additional studies using immunofluorescent antibody staining demonstrated the presence of p65 (a subunit of NF‐κB) only in muscle fibres containing centrally located nuclei, suggesting that NF‐kB was only active in regenerating muscle fibres.The aim of this study was to determine the extent and nature of activation of NF‐kB during regeneration in a well established mouse model of muscle degeneration and regeneration using the myotoxin, barium chloride (BaCl‐2‐). BaCl‐2‐ was injected into the extensor digitorum longus (EDL) muscles of adult (8 months) and old (22 month) wild‐type (WT) C57BL/6 mice. At defined time points the muscles were quickly excised, weighed and frozen in OCT for transverse sectioning. Changes in muscle morphology were observed through haemotoxylin and eosin staining while fluorescently labelled antibodies against p65 targeted the cellular localization of NF‐κB.Centrally located nuclei were present in the majority of the fibres at 14, 28 and 60 days post BaCl2 injection. Nuclear translocation of p65 was seen 14 and 28 days post BaCl2 injection indicating activation of the canonical NF‐κB pathway in regenerating fibres.The results of these experiments reveal an association between muscle fibre regeneration and activation of the canonical NF‐κB pathway. Further studies will determine the effect of activation of NF‐kB during regeneration on inflammatory gene expression and compare with activation in ageing models.Support or Funding InformationFunded by the National Institutes of Health (NIA).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.