Cyclic compressive loading as an intervention for skeletal muscle atrophy and imp

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DESCRIPTION (provided by applicant): Aging is associated with a decreased ability to recover muscle mass and strength after periods of inactivity, to which elderly are often subjected, resulting in frailty and functional dependence. Skeletal muscle is not only critically important for the development of force, but also serves as a major protein reservoir and is an important predictor of mobility, susceptibility to injury, and mortality. Therefore, it is criticaly important to design interventions to attenuate the decrease in muscle size during periods of disuse and to aid in the regrowth of atrophied muscle. Underlying mechanisms for the diminished capacity of muscle to regrow after disuse in the elderly are still largely unknown, but could be related to alterations in the inflammatory processes associated with recovery from atrophy. Massage therapy is used in clinical settings to aid in the repair of inflammatory conditions in muscles and we have found that massage in the form of cyclic compressive loading (CCL) positively modulates the immune response in muscle and aids in the repair of muscle injury and restoration of function in young animals. However, the effect of massage therapy on muscle atrophy and regrowth in the aged is completely unexplored. Therefore, we hypothesize that CCL is beneficial for the maintenance of muscle size during disuse-induced atrophy and will improve the impaired regrowth response in aged rats. We will investigate this hypothesis with two specific aims. In Aim 1 we hypothesize that CLL attenuates muscle mass lost during disuse-induced atrophy through actions on protein turnover pathways. Male Fischer 344/Brown Norway rats at 10 and 30 months of age will be hind limb suspended for 14 days to induce atrophy. CCL will be applied at two different loads in different groups of rats to gastrocnemius muscles of one leg during hind limb suspension. Changes in muscle size protein synthesis, markers of muscle protein synthesis and degradation, and force generating capacity will be measured. In Aim 2 we hypothesize that CCL will improve regrowth of muscle in aged rats through its immunomodulatory actions. Rats at 10 and 30 months of age will be hindlimb suspended for 14 days followed by ambulation for 1, 2, 4 or 14 days. CCL will be applied at two different loads to gastrocnemius muscle of one leg starting immediately after reambulation to assess the effect of CCL on recovery of muscle size after atrophy. Muscles will be assessed for size, immune cell infiltration, degradation and regeneration, and protein synthesis and degradation markers, as well as force generating capacity. The experiments proposed in this application will indicate whether massage therapy is beneficial for muscle maintenance in general and muscle size and strength restoration in the aged in particular. The age- associated diminished capacity to recover muscle mass lost during disuse is of great clinical importance and it is critically important to develop strategies that can prevent inactivity-induced atrophy or aid in the recovery of muscle mass lost during disuse. If our results prove beneficial, massage can be directly applied clinically for the maintenance and restoration of muscle size and strength.