Figure 6.

Key signaling pathways involved in testosterone-mediated mitigation of sarcopenia in aging. Testosterone, though suppression myostatin, inhibits JNK but stimulates Akt signaling. Suppression of JNK promotes muscle growth by not only inhibiting muscle cell apoptosis but also stimulating cellular proliferation by attenuating myostatin-induced up-regulation of p21. Akt can promote muscle growth through direct activation of Notch signaling (67) as well as through modulation of multiple signaling molecules involved in both apoptotic and survival pathways in muscle remodeling (24). Akt can also restrain caspase-2-mediated death pathway and promote muscle growth by stimulation of cellular metabolism (47). Thus, testosterone through stimulation of survival pathway together with the inhibition of death pathway possibly restores the microenvironment and promotes muscle growth in aging.