Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity.

Muhammad Khadeesh Bin Imtiaz, Baptiste N Jaeger, Sara Bottes, Raquel A C Machado, Mojca Vidmar, Darcie L Moore, Sebastian Jessberger

Cell stem cell 2021 May 06

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Neural stem cells (NSCs) generate neurons throughout life in the hippocampal dentate gyrus. With advancing age, levels of neurogenesis sharply drop, which has been associated with a decline in hippocampal memory function. However, cell-intrinsic mechanisms mediating age-related changes in NSC activity remain largely unknown. Here, we show that the nuclear lamina protein lamin B1 (LB1) is downregulated with age in mouse hippocampal NSCs, whereas protein levels of SUN-domain containing protein 1 (SUN1), previously implicated in Hutchinson-Gilford progeria syndrome (HGPS), increase. Balancing the levels of LB1 and SUN1 in aged NSCs restores the strength of the endoplasmic reticulum diffusion barrier that is associated with segregation of aging factors in proliferating NSCs. Virus-based restoration of LB1 expression in aged NSCs enhances stem cell activity in vitro and increases progenitor cell proliferation and neurogenesis in vivo. Thus, we here identify a mechanism that mediates age-related decline of neurogenesis in the mammalian hippocampus. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Muhammad Khadeesh Bin Imtiaz, Baptiste N Jaeger, Sara Bottes, Raquel A C Machado, Mojca Vidmar, Darcie L Moore, Sebastian Jessberger. Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity. Cell stem cell. 2021 May 06;28(5):967-977.e8