Cellular Basis for ADT-Induced Acceleration of Sarcopenia
Technical Report,30 Sep 2014,29 Sep 2015
University of Rochester Rochester United States
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Currently the only proposed treatment for ADT-induced muscle wasting is exercise based interventions. However, the intensity of exercise required coupled with the susceptibility of prostate cancer patients to fractures due to 1 the already high incidence of bone metastasis and 2 ADT-induced acceleration in osteoporosis emphasizes the need for other therapies. In order to devise effective therapies, an understanding as to how ADT results in severe and debilitating loss in skeletal muscle and overall performance is required. The goal of this proposal is to employ pre-clinical models to gain insight into the cellular and molecular mechanisms responsible for ADT-induced loss of skeletal muscle regenerative potential. Specifically, the aims are designed to address how ADT affects the maintenance and function of Pax7 expressing resident stem cells of skeletal muscle, satellite cells SCs, which are absolutely required for optimal skeletal muscle growth and regeneration. The completion of the aims outlined in this proposal should provide insights into the extent to which abnormalities in stem cell function and thereby regenerative capability contribute to the acceleration of sarcopenia observed in prostate cancer patients undergoing ADT. In addition, this proposal intends to employ pre-clinical genetic strategies to determine the utility of stimulating the expression of genes known to maintain SC number and function for the ability to resist ADT-induced loss of skeletal muscle regeneration. Ultimately, the elucidation of regenerative strategies to circumvent androgen supplementation to sustain skeletal muscle should be of tremendous benefit towards research that strives to improve the quality of life and well-being of prostate cancer patients receiving ADT.