Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/44356
Title: Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus
Authors: MATIAS, IsadoraDINIZ, Luan PereiraDAMICO, Isabella VivariniARAUJO, Ana Paula BergamoNEVES, Lais da SilvaVARGAS, GabrieleLEITE, Renata E. P.SUEMOTO, Claudia K.NITRINI, RicardoJACOB-FILHO, WilsonGRINBERG, Lea T.HOL, Elly M.MIDDELDORP, JinteGOMES, Flavia Carvalho Alcantara
Citation: AGING CELL, v.21, n.1, article ID e13521, 18p, 2022
Abstract: 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.
Appears in Collections:

Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - FM/MNE
Departamento de Neurologia - FM/MNE

Artigos e Materiais de Revistas Científicas - FM/MPT
Departamento de Patologia - FM/MPT

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - LIM/15
LIM/15 - Laboratório de Investigação em Neurologia

Artigos e Materiais de Revistas Científicas - LIM/22
LIM/22 - Laboratório de Patolologia Cardiovascular

Artigos e Materiais de Revistas Científicas - LIM/66
LIM/66 - Laboratório de Investigação Médica em Envelhecimento


Files in This Item:
File Description SizeFormat 
art_MATIAS_Loss_of_laminB1_and_defective_nuclear_morphology_are_2022.PDFpublishedVersion (English)2.78 MBAdobe PDFThumbnail
View/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.