Gdf11, also known as bone morphogenetic protein 11 (BMP11), is a member of the Transforming Growth Factor β superfamily. It plays crucial roles in embryogenesis, cell cycle control, apoptosis, and cell differentiation. Gdf11 is involved in lipid metabolism, inflammatory processes, and aging, and is strongly related to carcinogenesis [1,5,7,8].

In the brain, selective knockout of Gdf11 in post-mitotic excitatory neurons in mice induces brain-aging-related transcriptional changes, neuronal senescence, hyperexcitability, dendritic pruning, synaptic input impairment, memory deficits, and shortened lifespan, indicating that endogenous Gdf11 acts as a brake on excitatory neuronal senescence and brain aging [2]. Systemic administration of Gdf11 in aged mice improves memory, alleviates senescence and depression-like symptoms through enhancing neuronal autophagy, and analysis of sera from young adults with major depressive disorder shows reduced Gdf11 levels [3]. In a murine model of corticosterone-induced depression-like phenotype, Gdf11 attenuates depressive-like behavior. In diabetic mice, topical application of Gdf11 promotes wound healing by stimulating endothelial progenitor cell mobilization and neovascularization mediated by the HIF-1ɑ-VEGF/SDF-1ɑ pathway [4]. In osteoarthritis, Gdf11 conditional knockout mice show NLRP3 inflammasome activation, inflammation, and metabolic dysfunction, while intra-articular administration of recombinant human Gdf11 alleviates OA pathogenesis, suggesting Gdf11 can suppress TNF-α-induced inflammation and cartilage degeneration by inhibiting NLRP3 inflammasome activation [6].

In conclusion, Gdf11 is a key regulator in multiple biological processes. Gene knockout and conditional knockout mouse models have revealed its important roles in brain aging, depression, diabetic wound healing, and osteoarthritis. These findings suggest Gdf11 could be a potential therapeutic target for related diseases.