Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke

[EN] In recent years, evidence of the existence of cellular senescence in the central nervous system has accumulated. In ischemic stroke, cellular senescence has been suggested as an unidentified pathophysiological mechanism, prompting research into the neuroprotective potential of senolytic drugs....

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Autores: Baixauli-Martín, Júlia, Burguete, Mª Consuelo, López-Morales, Mikahela Andrea, Castelló, María, Aliena-Valero, Alicia, Jover, Teresa, Falahatgaroshibi, Dianoush, Torregrosa, Germán, Salom, Juan B.
Tipo de documento: artigo
Data de publicação:2025
País:España
Recursos:Universitat Politècnica de València (UPV)
Repositório:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglês
OAI Identifier:oai:riunet.upv.es:10251/220643
Acesso em linha:https://riunet.upv.es/handle/10251/220643
Access Level:Acceso aberto
Palavra-chave:Cell cycle arrest
Cellular senescence
DNA damage
Ischemic stroke
Middle cerebral artery occlusion
Senescence-associated beta-galactosidase
Senescence-associated secretory phenotype
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spelling Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic StrokeBaixauli-Martín, JúliaBurguete, Mª ConsueloLópez-Morales, Mikahela AndreaCastelló, MaríaAliena-Valero, AliciaJover, TeresaFalahatgaroshibi, DianoushTorregrosa, GermánSalom, Juan B.Cell cycle arrestCellular senescenceDNA damageIschemic strokeMiddle cerebral artery occlusionSenescence-associated beta-galactosidaseSenescence-associated secretory phenotype[EN] In recent years, evidence of the existence of cellular senescence in the central nervous system has accumulated. In ischemic stroke, cellular senescence has been suggested as an unidentified pathophysiological mechanism, prompting research into the neuroprotective potential of senolytic drugs. This study aims to provide spatio-temporal evidence of the existence of brain senescence following ischemic stroke and to elucidate the involved pathways and cell types. We focused on the most established markers of senescence: cell cycle arrest (p16, p21); lysosomal activity (senescence-associated beta-galactosidase [SA-beta-gal]); the senescence-associated secretory phenotype ([SASP]; Interleukin-6 [IL-6], Interleukin-1 beta [IL-1 beta], Tumor necrosis factor [TNF]); and DNA/nuclear damage (Checkpoint kinase 1 [Chk1], Checkpoint kinase 2 [Chk2], Lamin B1 [LB1]). Male Wistar rats underwent 60 min of transient middle cerebral artery occlusion, followed by 24 h and 3, 7, and 14 days of recovery. Our results show significant increases in p16 expression, particularly in neurons and microglia/macrophages; SA-beta-gal accumulation in the infarcted tissue; significant increases in SASP markers as early as 24 h after reperfusion; and significant changes in Chk1, Chk2, and LB1 at 14 days. Overall, our findings lend support to the existence of senescence after ischemic stroke in neurons and microglia/macrophages. However, there is still room to gain further insight into the role of senescence in the pathophysiology of ischemic stroke and in the implementation of successful senolytic therapy.This research was funded by the Ministerio de Ciencia e Innovacion, grant number PID2020-119603RB-I00; by the Instituto de Salud Carlos III, grant number RD21/0006/0014 (co-funded by European Regional Development Fund "A way to make Europe"); and by the Conselleria de Innovacion, Universidades, Ciencia y Sociedad Digital, grant number CIAICO/2022/248.MDPIGeneralitat ValencianaInstituto de Salud Carlos IIIAgencia Estatal de InvestigaciónEuropean Regional Development FundRepositorio Institucional de la Universitat Politècnica de València Riunet20252025-03-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://riunet.upv.es/handle/10251/220643reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PID2020-119603RB-I00 SENESCENCIA CELULAR CEREBRAL COMO CONDICION ASOCIADA AL ENVEJECIMIENTO QUE AGRAVA EL DAÑO CEREBRAL INDUCIDO POR ICTUS: UNA OPORTUNIDAD PARA LOS FARMACOS SENOLITICOSGeneralitat Valenciana https://doi.org/10.13039/501100003359 CIAICO%2F2022%2F248Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD21%2F0006%2F0014open accesshttp://purl.org/coar/access_right/c_abf2Reconocimiento (by)http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riunet.upv.es:10251/2206432026-06-13T07:49:27Z
dc.title.none.fl_str_mv Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke
title Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke
spellingShingle Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke
Baixauli-Martín, Júlia
Cell cycle arrest
Cellular senescence
DNA damage
Ischemic stroke
Middle cerebral artery occlusion
Senescence-associated beta-galactosidase
Senescence-associated secretory phenotype
title_short Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke
title_full Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke
title_fullStr Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke
title_full_unstemmed Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke
title_sort Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke
dc.creator.none.fl_str_mv Baixauli-Martín, Júlia
Burguete, Mª Consuelo
López-Morales, Mikahela Andrea
Castelló, María
Aliena-Valero, Alicia
Jover, Teresa
Falahatgaroshibi, Dianoush
Torregrosa, Germán
Salom, Juan B.
author Baixauli-Martín, Júlia
author_facet Baixauli-Martín, Júlia
Burguete, Mª Consuelo
López-Morales, Mikahela Andrea
Castelló, María
Aliena-Valero, Alicia
Jover, Teresa
Falahatgaroshibi, Dianoush
Torregrosa, Germán
Salom, Juan B.
author_role author
author2 Burguete, Mª Consuelo
López-Morales, Mikahela Andrea
Castelló, María
Aliena-Valero, Alicia
Jover, Teresa
Falahatgaroshibi, Dianoush
Torregrosa, Germán
Salom, Juan B.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Generalitat Valenciana
Instituto de Salud Carlos III
Agencia Estatal de Investigación
European Regional Development Fund
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Cell cycle arrest
Cellular senescence
DNA damage
Ischemic stroke
Middle cerebral artery occlusion
Senescence-associated beta-galactosidase
Senescence-associated secretory phenotype
topic Cell cycle arrest
Cellular senescence
DNA damage
Ischemic stroke
Middle cerebral artery occlusion
Senescence-associated beta-galactosidase
Senescence-associated secretory phenotype
description [EN] In recent years, evidence of the existence of cellular senescence in the central nervous system has accumulated. In ischemic stroke, cellular senescence has been suggested as an unidentified pathophysiological mechanism, prompting research into the neuroprotective potential of senolytic drugs. This study aims to provide spatio-temporal evidence of the existence of brain senescence following ischemic stroke and to elucidate the involved pathways and cell types. We focused on the most established markers of senescence: cell cycle arrest (p16, p21); lysosomal activity (senescence-associated beta-galactosidase [SA-beta-gal]); the senescence-associated secretory phenotype ([SASP]; Interleukin-6 [IL-6], Interleukin-1 beta [IL-1 beta], Tumor necrosis factor [TNF]); and DNA/nuclear damage (Checkpoint kinase 1 [Chk1], Checkpoint kinase 2 [Chk2], Lamin B1 [LB1]). Male Wistar rats underwent 60 min of transient middle cerebral artery occlusion, followed by 24 h and 3, 7, and 14 days of recovery. Our results show significant increases in p16 expression, particularly in neurons and microglia/macrophages; SA-beta-gal accumulation in the infarcted tissue; significant increases in SASP markers as early as 24 h after reperfusion; and significant changes in Chk1, Chk2, and LB1 at 14 days. Overall, our findings lend support to the existence of senescence after ischemic stroke in neurons and microglia/macrophages. However, there is still room to gain further insight into the role of senescence in the pathophysiology of ischemic stroke and in the implementation of successful senolytic therapy.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-03-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://riunet.upv.es/handle/10251/220643
url https://riunet.upv.es/handle/10251/220643
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PID2020-119603RB-I00 SENESCENCIA CELULAR CEREBRAL COMO CONDICION ASOCIADA AL ENVEJECIMIENTO QUE AGRAVA EL DAÑO CEREBRAL INDUCIDO POR ICTUS: UNA OPORTUNIDAD PARA LOS FARMACOS SENOLITICOS
Generalitat Valenciana https://doi.org/10.13039/501100003359 CIAICO%2F2022%2F248
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD21%2F0006%2F0014
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento (by)
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento (by)
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
instname:Universitat Politècnica de València (UPV)
instname_str Universitat Politècnica de València (UPV)
reponame_str RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
collection RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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