SMAD2 and sarcopenia: Notably, these growth differentiation factors demonstrate opposing pathophysiological effects: GDF11 overexpression paradoxically induces muscle wasting through activin receptor type IIB (ActRIIB)-SMAD2/3 hyperactivation (36), whereas GDF15 consistently promotes sarcopenia via glial cell line-derived neurotrophic factor receptor alpha-like (GFRAL)-mediated appetite suppression and energy imbalance.