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Disclosed herein are compositions and methods for the treatment of skeletal muscle and/or the protection of skeletal muscle against injury. The adenosine A3 receptor has been identified as a new therapeutic target for the treatment of skeletal muscle. Adenosine A3 receptor agonists are used treat subjects with skeletal muscle ischemia and reperfusion (I/R) injuries, individuals with skeletal muscle disorders, and individuals suffering from skeletal muscle injury resulting from physical exertion.