Klotho is an anti-aging protein with multiple functions in maintaining homeostasis within the central nervous system (CNS). Klotho-induced neurogenesis and oligodendrogenesis play a critical role in myelination, neuroplasticity, and hippocampus-dependent cognition. In this context, the objective of this review is to synthesize well-established information about the mechanisms through which Klotho influences neurogenesis and oligodendrogenesis. Previous studies have demonstrated that Klotho regulates adult neurogenesis, stimulates the proliferation of neural progenitor cells (NPCs), promotes the differentiation of NPCs into neurons, and facilitates neuronal maturation and dendritic arborization. Additionally, Klotho stimulates oligodendrocyte differentiation and maturation, as well as myelination throughout life. The reviewed evidence suggests that Klotho influences cell fate decisions during both development and adulthood and has a modulatory role in neuronal fate determination from embryonic stem cells in neurogenesis and oligodendrogenesis. Therefore, Klotho may represent a promising therapeutic target for neuroprotection, including the prevention of neurodevelopmental and neurodegenerative diseases.
Possebom et al. (2026) studied this question.