Cargando…
Loss of lamin‐B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus
The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age‐related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age‐...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761005/ https://www.ncbi.nlm.nih.gov/pubmed/34894056 http://dx.doi.org/10.1111/acel.13521 |
_version_ | 1784633443169075200 |
---|---|
author | Matias, Isadora Diniz, Luan Pereira Damico, Isabella Vivarini Araujo, Ana Paula Bergamo Neves, Laís da Silva Vargas, Gabriele Leite, Renata E. P. Suemoto, Claudia K. Nitrini, Ricardo Jacob‐Filho, Wilson Grinberg, Lea T. Hol, Elly M. Middeldorp, Jinte Gomes, Flávia Carvalho Alcantara |
author_facet | Matias, Isadora Diniz, Luan Pereira Damico, Isabella Vivarini Araujo, Ana Paula Bergamo Neves, Laís da Silva Vargas, Gabriele Leite, Renata E. P. Suemoto, Claudia K. Nitrini, Ricardo Jacob‐Filho, Wilson Grinberg, Lea T. Hol, Elly M. Middeldorp, Jinte Gomes, Flávia Carvalho Alcantara |
author_sort | Matias, Isadora |
collection | PubMed |
description | The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age‐related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age‐associated neurodegenerative diseases, but little is known about whether this process also occurs in physiological aging, as well as its functional implication. Here, we investigated astrocyte senescence in vitro, in old mouse brains, and in post‐mortem human brain tissue of elderly. We identified a significant loss of lamin‐B1, a major component of the nuclear lamina, as a hallmark of senescent astrocytes. We showed a severe reduction of lamin‐B1 in the dentate gyrus of aged mice, including in hippocampal astrocytes, and in the granular cell layer of the hippocampus of post‐mortem human tissue from non‐demented elderly. The lamin‐B1 reduction was associated with nuclear deformations, represented by an increased incidence of invaginated nuclei and loss of nuclear circularity in senescent astrocytes in vitro and in the aging human hippocampus. We also found differences in lamin‐B1 levels and astrocyte nuclear morphology between the granular cell layer and polymorphic layer in the elderly human hippocampus, suggesting an intra‐regional‐dependent aging response of human astrocytes. Moreover, we described senescence‐associated impaired neuritogenic and synaptogenic capacity of mouse astrocytes. Our findings show that reduction of lamin‐B1 is a conserved feature of hippocampal cells aging, including astrocytes, and shed light on significant defects in nuclear lamina structure which may contribute to astrocyte dysfunctions during aging. |
format | Online Article Text |
id | pubmed-8761005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87610052022-01-20 Loss of lamin‐B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus Matias, Isadora Diniz, Luan Pereira Damico, Isabella Vivarini Araujo, Ana Paula Bergamo Neves, Laís da Silva Vargas, Gabriele Leite, Renata E. P. Suemoto, Claudia K. Nitrini, Ricardo Jacob‐Filho, Wilson Grinberg, Lea T. Hol, Elly M. Middeldorp, Jinte Gomes, Flávia Carvalho Alcantara Aging Cell Original Papers The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age‐related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age‐associated neurodegenerative diseases, but little is known about whether this process also occurs in physiological aging, as well as its functional implication. Here, we investigated astrocyte senescence in vitro, in old mouse brains, and in post‐mortem human brain tissue of elderly. We identified a significant loss of lamin‐B1, a major component of the nuclear lamina, as a hallmark of senescent astrocytes. We showed a severe reduction of lamin‐B1 in the dentate gyrus of aged mice, including in hippocampal astrocytes, and in the granular cell layer of the hippocampus of post‐mortem human tissue from non‐demented elderly. The lamin‐B1 reduction was associated with nuclear deformations, represented by an increased incidence of invaginated nuclei and loss of nuclear circularity in senescent astrocytes in vitro and in the aging human hippocampus. We also found differences in lamin‐B1 levels and astrocyte nuclear morphology between the granular cell layer and polymorphic layer in the elderly human hippocampus, suggesting an intra‐regional‐dependent aging response of human astrocytes. Moreover, we described senescence‐associated impaired neuritogenic and synaptogenic capacity of mouse astrocytes. Our findings show that reduction of lamin‐B1 is a conserved feature of hippocampal cells aging, including astrocytes, and shed light on significant defects in nuclear lamina structure which may contribute to astrocyte dysfunctions during aging. John Wiley and Sons Inc. 2021-12-10 2022-01 /pmc/articles/PMC8761005/ /pubmed/34894056 http://dx.doi.org/10.1111/acel.13521 Text en © 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Papers Matias, Isadora Diniz, Luan Pereira Damico, Isabella Vivarini Araujo, Ana Paula Bergamo Neves, Laís da Silva Vargas, Gabriele Leite, Renata E. P. Suemoto, Claudia K. Nitrini, Ricardo Jacob‐Filho, Wilson Grinberg, Lea T. Hol, Elly M. Middeldorp, Jinte Gomes, Flávia Carvalho Alcantara Loss of lamin‐B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus |
title | Loss of lamin‐B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus |
title_full | Loss of lamin‐B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus |
title_fullStr | Loss of lamin‐B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus |
title_full_unstemmed | Loss of lamin‐B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus |
title_short | Loss of lamin‐B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus |
title_sort | loss of lamin‐b1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761005/ https://www.ncbi.nlm.nih.gov/pubmed/34894056 http://dx.doi.org/10.1111/acel.13521 |
work_keys_str_mv | AT matiasisadora lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT dinizluanpereira lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT damicoisabellavivarini lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT araujoanapaulabergamo lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT neveslaisdasilva lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT vargasgabriele lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT leiterenataep lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT suemotoclaudiak lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT nitriniricardo lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT jacobfilhowilson lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT grinbergleat lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT holellym lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT middeldorpjinte lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus AT gomesflaviacarvalhoalcantara lossoflaminb1anddefectivenuclearmorphologyarehallmarksofastrocytesenescenceinvitroandintheaginghumanhippocampus |