Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity
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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.
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Expression of lamin B1 declines in old NSCs, and restoration of lamin B1 expression is sufficient to increase old NSC proliferation and neurogenesis.
“Finally, expression of lamin B1, a key component of the nuclear architecture involved in epigenomic maintenance103, declines in old NSCs, and restoration of lamin B1 expression is sufficient to increase old NSC proliferation and neurogenesis104.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [104]
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- Authors
- bin Imtiaz, M. K., Jaeger, B. N., Bottes, S., Machado, R. A. C., Vidmar, M., Moore, D. L., & Jessberger, S.
- Affiliations
- University of Zurich (CH)
- University of Wisconsin–Madison (US)
- Corresponding author
- Moore, Darcie L.
- Jessberger, Sebastian
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 28
- Issue
- 5
- Pages
- 967-977.e8
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W3132495570
- Cited by
- 83
- References
- 60
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 20 · 2023: 14 · 2022: 13 · 2021: 5
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Foundation for the National Institutes of Health
- European Research Council
- Helmut Horten Stiftung
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- lamin B1, SUN1, nuclear lamina, neural stem cells, hippocampal neurogenesis, aging, Hutchinson-Gilford progeria syndrome, stem cell proliferation
- MeSH terms
- Aging, Animals, Hippocampus, Progeria, Lamin Type B, Mice, Neurogenesis, Neural Stem Cells
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