Nerve regeneration by interferon intervention in aging brain

Neural stem cells (NSCs) are shielded from viral infection by interferon (IFN) defense. As individuals age, activation of NSC decreases with a significant decline of stemness marker Sex‐determining region Y box 2 (Sox2) while IFN signaling enhances (Kalamakis et al, 2019). Given that low‐level type‐I IFN under normal physiological conditions can promote dormant hematopoietic stem cell differentiation (Baldridge et al, 2010), whether there is an inner connection between IFN signaling and NSC function remains elusive. In this issue of EMBO Molecular Medicine, Carvajal Ibanez et al (2023) reveal that IFN‐β, a type‐I interferon, induces cell‐type‐specific interferon‐stimulated genes (ISGs) and regulates global protein synthesis by orchestrating mTOR1 activity and stem cell cycle that retain NSCs at the G(0) phase and repress Sox2 expression. As a consequence, NSCs exit the activation state and become inclined to differentiation.