The Immateriality of Circulating GDF11

Abstract

Recent portrayals of growth differentiation factor (GDF)-11 as an endocrine fountain of youth fail to consider the competitive influences of myostatin, a homologous protein with true endocrine action that binds the identical receptor, activin receptor IIb (ActRIIb). Subsequent studies have disproven the original premise that circulating levels of GDF11, but not those of myostatin, decline with age as the exact opposite seems to be true. These latter studies also seriously question the validity of data presented in the previous reports and indicate that myostatin circulates at levels 500× greater than those of GDF11; yet, both ligands share nearly identical affinities for ActRIIb. The compromised striated muscle function, neurogenesis, and vascular remodeling that occur with advanced age are, therefore, not caused by reduced circulating GDF11 as it could never outcompete myostatin for shared receptor-binding sites.