Aging of the ventricular-subventricular zone neural stem cell niche

The adult mammalian central nervous system (CNS) maintains populations of neural stem cells (NSCs) with the capacity to proliferate, self-renew and differentiate into neurons and glia throughout life. NSCs are principally restricted to two discrete stem cell niches—the ventricular-subventricular zone (V-SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus. In health, neurons are the primary post-mitotic cell type generated by adult NSCs; a process termed adult neurogenesis. Adult-born neurons generated in the V-SVZ and SGZ of the rodent brain become functionally integrated into neural circuits required for olfactory discrimination and spatial learning and memory, respectively. Also, NSCs are responsive to states of neuropathology and serve pro-survival and regenerative roles in this context. Since NSCs are retained throughout life, this has raised the prospect that endogenous NSC function could be optimized for therapeutic benefit in the context of disease. Constraining this potential is an age-dependent decline in neurogenic activity and in the capacity of quiescent NSCs to respond to activation cues. Focusing on the V-SVZ NSC niche, this review highlights recent studies that bring to light vital mechanisms that underpin the age-dependent attrition of neurogenic activity in the mammalian CNS.