Hibernating squirrel muscle activates the endurance exercise pathway despite prolonged immobilization

► Hibernating 13-lined ground squirrels exhibit a shift to slow-twitch Type I muscle fibers. ► The muscle fiber switch is accompanied by an activation of the PGC-1α-mediated endurance exercise pathway. ► Increased antioxidant capacity without evidence of oxidative stress is seen in hibernating skeletal muscle. ► We observe a marked decline in apoptotic susceptibility, and enhanced mitochondrial metabolism. ► Activation of the PGC-1α-endurance exercise pathway can be achieved in vivo despite immobilization during hibernation.