Grant: Operating Grant

The causes of the age-related loss of muscle mass and function known as sarcopenia are unknown. Amongst the most frequently implicated culprits is an intrinsic defect in mitochondrial function, an idea supported by the up-regulation of mitochondrial-driven molecular signals that can cause muscle atrophy in aging muscle. Despite the appeal of this theory, alterations in mitochondrial function could be either a cause or an effect of other processes in aging muscle, and clarifying this will have an important role in dictating the therapeutic approach used in treating sarcopenia. In this respect, our recent data shows that denervation of aging muscle cells is arguably the most important cause of muscle cell atrophy. As such, the experiments proposed in this application will determine the extent to which denervation induces changes in mitochondrial function (wherein the mitochondria do not have a primary defect but are merely responding to upstream signals induced by denervation) versus the extent to which mitochondrial dsyfunction causes denervation in aging muscle (wherein the mitochondria have a specific defect that needs to be corrected to prevent denervation). The answer to this question will ultimately determine whether therapies for sarcopenia should be targeted at correcting defects in mitochondrial function versus being aimed at other processes that could cause denervation of aging muscle cells.