Transcriptional and epigenetic dysregulation impairs generation of proliferative neural stem and progenitor cells during brain aging.

ABSTRACT: The decline in stem cell function during aging may affect the regenerative capacity of mammalian organisms; however, the gene regulatory mechanism underlying this decline remains unclear. Here we show that the aging of neural stem and progenitor cells (NSPCs) in the male mouse brain is characterized by a decrease in the generation efficacy of proliferative NSPCs rather than the changes in lineage specificity of NSPCs. We reveal that the downregulation of age-dependent genes in NSPCs drives cell aging by decreasing the population of actively proliferating NSPCs while increasing the expression of quiescence markers. We found that epigenetic deregulation of the MLL complex at promoters leads to transcriptional inactivation of age-dependent genes, highlighting the importance of the dynamic int

SUBMITTER: Li M 

PROVIDER: S-EPMC10947366 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature