Neural stem cell secretome: a secret key to unlocking the power of regeneration in the adult and aging brain.

Adult neurogenesis involves the activation of quiescent neural stem cells (qNSCs) to generate new neurons, which migrate and integrate into existing neural circuits. In addition to their role in neurogenesis, adult NSCs also secrete bioactive compounds collectively known as the secretome, which contribute to the regulation of this process. However, aging and neurodegenerative diseases impair neurogenesis by promoting a pro-inflammatory environment within the neurogenic niche. With age, NSCs become increasingly quiescent, leading to a decline in their secretory activity- a hallmark of aged NSCs. Enhancing the function of adult NSCs holds therapeutic potential for restoring brain function under these conditions. Specifically, reactivating quiescent NSCs and possibly eliminating senescent ones can boost neurogenesis and improve cognitive function in aging and neurodegenerative diseases. In this review, we explore the role of adult NSCs and their secretome in sustaining brain function throughout adulthood and aging. A comprehensive analysis of the literature sheds light onto how NSCs and their secretome influence neurogenesis, from activation and differentiation to integration into neural circuits. Targeting adult NSCs in aged and neurodegenerative models presents a promising strategy for brain function restoration.