Gdf11, also known as bone morphogenetic protein 11 (BMP11), is a member of the Transforming Growth Factor β superfamily. It plays crucial roles in various biological processes, such as embryogenesis, cell cycle control, apoptosis, and is involved in lipid metabolism, inflammatory processes, and aging [2,5]. Gdf11 mainly targets cells with stemness features, regulating cell differentiation and maturation [2].

Selective knockout of Gdf11 in post-mitotic excitatory neurons in mice shapes the brain ageing-related transcriptional profile, induces neuronal senescence, hyperexcitability, dendrite pruning, synaptic input impairment, object recognition memory loss, and shortens lifespan, indicating its role in brain ageing and cognition [1]. In vitro, Gdf11 deletion causes cellular senescence in Neuro-2a cells [1]. Systemic Gdf11 administration in aged mice improves memory, alleviates senescence and depression-like symptoms through stimulating neuronal autophagy, and reduces the activity of mammalian target of rapamycin (mTOR) [3]. Conditional knockout of Gdf11 in mice shows that its loss leads to NLRP3 inflammasome activation, inflammation, and metabolic dysfunction in chondrocytes, and intra-articular administration of recombinant human Gdf11 alleviates osteoarthritis pathogenesis [4].

In conclusion, Gdf11 is essential in multiple biological processes. Studies using Gdf11 KO/CKO mouse models have revealed its significance in brain-related diseases like ageing-associated cognitive decline and depression, as well as in osteoarthritis. These models have been instrumental in understanding the role of Gdf11 in specific disease conditions, providing insights into potential therapeutic strategies.