biostudies-literatureWu YSwiss National Science FoundationEuropean Research Council380-390https://www.ebi.ac.uk/biostudies/studies/S-EPMC10154232biostudies-literatureUnknown3(4)Neural stem cells (NSCs) generate new neurons throughout life in the mammalian hippocampus¹. Advancing age leads to a decline in neurogenesis, which is associated with impaired cognition^2,3. The cellular mechanisms causing reduced neurogenesis with advancing age remain largely unknown. We genetically labeled NSCs through conditional recombination driven by the regulatory elements of the stem-cell-expressed gene GLI family zinc finger 1 (Gli1) and used chronic intravital imaging to follow individual NSCs and their daughter cells over months within their hippocampal niche^4,5. We show that aging affects multiple steps, from cell cycle entry of quiescent NSCs to determination of the number of surviving cells, ultimately causing reduced clonal output of individuNature agingChronic in vivo imaging defines age-dependent alterations of neurogenesis in the mouse hippocampus.PMC10154232209272157859Zehnder CFisch RHelmchen FPilz GASimons BDBottes SWu YCole JDJessberger SfalseChronic in vivo imaging defines age-dependent alterations of neurogenesis in the mouse hippocampus.Neural stem cells (NSCs) generate new neurons throughout life in the mammalian hippocampus¹. Advancing age leads to a decline in neurogenesis, which is associated with impaired cognition^2,3. The cellular mechanisms causing reduced neurogenesis with advancing age remain largely unknown. We genetically labeled NSCs through conditional recombination driven by the regulatory elements of the stem-cell-expressed gene GLI family zinc finger 1 (Gli1) and used chronic intravital imaging to follow individual NSCs and their daughter cells over months within their hippocampal niche^4,5. We show that aging affects multiple steps, from cell cycle entry of quiescent NSCs to determination of the number of surviving cells, ultimately causing reduced clonal output of individu2023-01-01T00:00:00Z2023 Apr2025-04-21T22:48:16.72Z2025-04-05T18:55:57.74ZS-EPMC101542323711778710.1038/s43587-023-00370-9