GDF11

Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP11), is a member of the transforming growth factor-β superfamily and is closely related to the family member myostatin (also known as GDF8). ^[1] In addition to its roles in embryonic development, GDF11 has drawn much interest for its proposed roles in other processes such as aging. ^[2] GDF11 was first identified in 2004 due to its reported ability to rejuvenate the function of multiple organs in old mice. ^[1]

GDF11 binds and activates specific receptor complexes and transmits signals through the TGFβ-Smad pathway and the bone morphogenic protein (BMP)-Smad pathway. ^[3] In the context of aging, GDF11 has been reported to promote vascular and neural plasticity of the central nervous system and to function as a proneurogenic and proangiogenic factor. ^[3] In the aged brain, exogenous peripherally delivered GDF11 may enhance neurogenesis and angiogenesis, in contrast to a predominantly negative influence on neurogenesis in the developing central nervous system. ^[4]

Parabiosis, the surgical linking of circulations between old and young mice, was employed to identify GDF11 as an anti-hypertrophic factor that appears to rejuvenate the aging murine heart. ^[5] The heralded rejuvenating effects of GDF11 have been seriously questioned by many studies that do not support the idea that restoring levels of GDF11 in aging improves overall organ structure and function. ^[1] Some controversy exists regarding the role of GDF11 in biological processes and whether it will serve as a therapeutic agent, with much of the controversy attributed to technical problems such as the specificity of GDF11 antibodies and confusion with its closer family member myostatin. ^{[2] [6]} Several studies have described the involvement of GDF11 in fibrotic processes in various organs, so its role as a rejuvenating factor versus a pro-fibrotic factor remains unresolved. ^[1]

The level of circulating GDF11 has been reported to correlate with the outcomes of patients with cardiovascular diseases, cancer and uremia, suggesting it is a candidate biomarker of disease. ^[2] GDF11 has been strongly related to carcinogenesis, and it can promote cancer growth in the colon or inhibit cell proliferation in breast cancer depending on context. ^[7] Caution is warranted with GDF11 because it appears to negatively influence muscle health and body composition. ^[4]