PPARGC1A and Atrophy: Notably, Activin-A inhibits PGC1α expression in ECs within muscle tissue, which disrupts vascular integrity, leading to vascular leakage and muscle loss.335 This finding is consistent with studies showing that PGC1α overexpression in myocytes can partially inhibit age-related muscle atrophy by activating mitochondrial oxidative metabolism and neovascularization.336