Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus.

Autor: Matias I; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Diniz LP; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Damico IV; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Araujo APB; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Neves LDS; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Vargas G; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Leite REP; Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.; Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil., Suemoto CK; Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.; Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil., Nitrini R; Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil., Jacob-Filho W; Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.; Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil., Grinberg LT; Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, California, USA.; Department of Pathology, University of California San Francisco, San Francisco, California, USA., Hol EM; Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands., Middeldorp J; Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.; Department of Immunobiology, Biomedical Primate Research Center, Rijswijk, The Netherlands., Gomes FCA; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2022 Jan; Vol. 21 (1), pp. e13521. Date of Electronic Publication: 2021 Dec 10.
DOI: 10.1111/acel.13521
Abstrakt: 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.
(© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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