G.P.118 Targeting sarcopenia: Molecular basis of denervation of aged muscles and benefits of life-long exercise

With ageing, the progressive loss of muscle mass and function (sarcopenia) results in frailty, loss of independence and is a major cause of increased falls and fractures. The precise reasons for sarcopenia are unclear. We have previously described the time course of sarcopenia in female C57Bl/6J mice with significant loss of muscle mass at 24 and 28months (m) of age (Shavlakadze et al., 2010: Biogerontology). Muscle function and maintenance of muscle mass require electrical stimulation by a nerve, yet denervation as a primary cause for sarcopenia has barely been considered. We have described altered morphology and striking denervation of neuromuscular junctions (NMJs) for muscles in geriatric (28m) compared to young (3m) female C57Bl/6J mice, using immunostaining of whole intact fast extensor digitorum longus (EDL) muscle (Chai et al., 2011: PlosONE). Myofibre type changes indicative of muscle denervation and re-innervation were observed in all muscles examined. However, there was no loss of alpha-motoneuron cell bodies in the lumbar spinal cord of geriatric (28m) mice. These data suggest that changes in the muscles per se are a primary cause of the age-related denervation. Establishing these baseline data for geriatric mice is essential in order to take full advantage of the wealth of genetically modified mice available to study sarcopenia, and for testing therapeutic interventions. Our molecular analyses of muscles from mice aged 3, 15, 24 and 28months aim to identify the molecular basis for this age-relate denervation. We have already demonstrated that life-long exercise significantly reduces sarcopenia (measured by loss of muscle mass) at 28months of age (unpublished) and we are investigating the molecular basis for the benefits of this exercise on ageing muscles with a focus on NMJ innervation.