Lamin B1 decline underlies age‐related loss of adult hippocampal neurogenesis.

Neurogenesis in the adult hippocampus declines with age, a process that has been implicated in cognitive and emotional impairments. However, the mechanisms underlying this decline have remained elusive. Here, we show that the age‐dependent downregulation of lamin B1, one of the nuclear lamins in adult neural stem/progenitor cells (ANSPCs), underlies age‐related alterations in adult hippocampal neurogenesis. Our results indicate that higher levels of lamin B1 in ANSPCs safeguard against premature differentiation and regulate the maintenance of ANSPCs. However, the level of lamin B1 in ANSPCs declines during aging. Precocious loss of lamin B1 in ANSPCs transiently promotes neurogenesis but eventually depletes it. Furthermore, the reduction of lamin B1 in ANSPCs recapitulates age‐related anxiety‐like behavior in mice. Our results indicate that the decline in lamin B1 underlies stem cell aging and impacts the homeostasis of adult neurogenesis and mood regulation. SYNOPSIS: Mutations in the nuclear envelope protein lamin B1 are linked to cellular aging and senescence. Here, lamin B1 ablation in adult neural stem/progenitor cells (ANSPCs) in mice is shown to disrupt neurogenesis, leading to aging‐related behavioral changes. Lamin B1 is highly expressed in ANSPCs, but selectively declines with age.Conditional knockout of lamin B1 in ANSPCs leads to premature differentiation and reduction of adult hippocampal neurogenesis.Lamin B1 knockout leads to age‐related anxiety‐like behaviours in mice.Overexpression of lamin B1 suppresses ANSPC differentiation. [ABSTRACT FROM AUTHOR]