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Muscle is a multifunctional tissue that must balance various processes to maintain homeostasis.This intramuscular balance must also be balanced against processes in other tissues to maintain overall homeostasis.It is therefore unsurprising that spending on musculoskeletal disorders accounted for 7.7% of US GDP in 2004 and that severe muscle wasting can be a direct contributor to death (for example, cancer cachexia).We have developed C.elegans into a system in which to study the intramuscular signals that regulate protein degradation.We have focused on protein degradation as it is a process that is required for muscle atrophy to occur and because we know very little of how extramuscular signals regulate the four key proteolytic systems within muscle.Utilizing various transgenic strains,we performed an analysis of RNAi effects on muscle proteostasis (balance of protein synthesis and degradation),muscle protein degradation and sarcomere and mitochondrial structure.Proteostasis was the most commonly affected process, followed by mitochondria morphology and sarcomere morphology.These observations fit with the hypothesis that proteostasis serves to provide a buffer against individual gene disruption.Accordingly, we frequently observe alterations in proteostasis in the absence of developmental/behavioural phenotypes.RNAi treatment of adults reveals that the majority of genes identified appear to be important in maintaining terminally differentiated muscle: RNAi against 53% of kinase genes and 52% of the phosphatase genes yields muscular defects (e.g.protein degradation or dystrophy(s)).As more than a third of the identified kinases and phosphatases are known to be expressed in human muscle, these may represent avenues for research aimed at therapeutic modulation of muscle homeostasis.