biostudies-literatureCorenblum MJArizona Biomedical Research CommissionEvelyn F. McKnight Brain Research FoundationNIEHS NIH HHSUniversity of Arizona725-36https://www.ebi.ac.uk/biostudies/studies/S-EPMC4933666biostudies-literatureUnknown15(4)Although it is known that the regenerative function of neural stem/progenitor cells (NSPCs) declines with age, causal mechanisms underlying this phenomenon are not understood. Here, we systematically analyze subventricular zone (SVZ) NSPCs, in various groups of rats across the aging spectrum, using in vitro and in vivo histological and behavioral techniques. These studies indicate that although NSPC function continuously declines with advancing age, there is a critical time period during middle age (13-15 months) when a striking reduction in NSPC survival and regeneration (proliferation and neuronal differentiation) occurs. The studies also indicate that this specific temporal pattern of NSPC deterioration is functionally relevant at a behavioral level and correlates with the decreasing exAging cellReduced Nrf2 expression mediates the decline in neural stem cell function during a critical middle-age period.PMC4933666T32 ES007091ADHS14‐082982P30 ES006694Harder BZhang DDCorenblum MJBarnes CAMadhavan LLong MRemley QWRay SfalseReduced Nrf2 expression mediates the decline in neural stem cell function during a critical middle-age period.Although it is known that the regenerative function of neural stem/progenitor cells (NSPCs) declines with age, causal mechanisms underlying this phenomenon are not understood. Here, we systematically analyze subventricular zone (SVZ) NSPCs, in various groups of rats across the aging spectrum, using in vitro and in vivo histological and behavioral techniques. These studies indicate that although NSPC function continuously declines with advancing age, there is a critical time period during middle age (13-15 months) when a striking reduction in NSPC survival and regeneration (proliferation and neuronal differentiation) occurs. The studies also indicate that this specific temporal pattern of NSPC deterioration is functionally relevant at a behavioral level and correlates with the decreasing ex2016-01-01T00:00:00Z2016 Aug2025-04-22T02:18:08.25Z2019-03-27T02:17:38ZS-EPMC49336662709537510.1111/acel.12482