Targeting senescent cells improves functional recovery after spinal cord injury
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/121435 |
Resumo: | Funding Information: We are grateful to A. Nascimento, A. Temudo, and J. Rino from the Bioimaging Unit for all of their precious advice. We thank the support given by the Fish and Rodent Facilities and the Histology and Comparative Pathology Laboratory, A. Ribeiro and C. de Sena-Tomás for critical reading of the manuscript, and M. Rebocho-da-Costa for help with the graphical abstract. D.P.d.C. was supported by a FCT PhD fellowship ( PD/BD/105770/2014 ). I.M. was supported by a FCT post-doctoral fellowship ( SFRH/BPD/118051/2016 ). A.M.C. was supported by a FCT fellowship ( PTDC/BOM-MED/3295/2014 ). A.F.D. was supported by CONGENTO LISBOA-01-0145-FEDER-022170 , co-financed by FCT (Portugal) and Lisboa2020 , under the PORTUGAL2020 agreement ( European Regional Development Fund ). D.N.-S. was supported by a FCT PhD fellowship ( SFRH/BD/138636/2018 ). D.C. was supported by a FCT PhD fellowship ( PD/BD/114179/2016 ). L.S. was supported by a FCT IF contract. The project leading to these results has received funding from a FCT grant ( PTDC/MED-NEU/30428/2017 ) and “la Caixa” Banking Foundation and FCT , I.P., under project code HR18-00187 . Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved. |
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Targeting senescent cells improves functional recovery after spinal cord injuryBiochemistry, Genetics and Molecular Biology(all)Funding Information: We are grateful to A. Nascimento, A. Temudo, and J. Rino from the Bioimaging Unit for all of their precious advice. We thank the support given by the Fish and Rodent Facilities and the Histology and Comparative Pathology Laboratory, A. Ribeiro and C. de Sena-Tomás for critical reading of the manuscript, and M. Rebocho-da-Costa for help with the graphical abstract. D.P.d.C. was supported by a FCT PhD fellowship ( PD/BD/105770/2014 ). I.M. was supported by a FCT post-doctoral fellowship ( SFRH/BPD/118051/2016 ). A.M.C. was supported by a FCT fellowship ( PTDC/BOM-MED/3295/2014 ). A.F.D. was supported by CONGENTO LISBOA-01-0145-FEDER-022170 , co-financed by FCT (Portugal) and Lisboa2020 , under the PORTUGAL2020 agreement ( European Regional Development Fund ). D.N.-S. was supported by a FCT PhD fellowship ( SFRH/BD/138636/2018 ). D.C. was supported by a FCT PhD fellowship ( PD/BD/114179/2016 ). L.S. was supported by a FCT IF contract. The project leading to these results has received funding from a FCT grant ( PTDC/MED-NEU/30428/2017 ) and “la Caixa” Banking Foundation and FCT , I.P., under project code HR18-00187 . Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.Persistent senescent cells (SCs) are known to underlie aging-related chronic disorders, but it is now recognized that SCs may be at the center of tissue remodeling events, namely during development or organ repair. In this study, we show that two distinct senescence profiles are induced in the context of a spinal cord injury between the regenerative zebrafish and the scarring mouse. Whereas induced SCs in zebrafish are progressively cleared out, they accumulate over time in mice. Depletion of SCs in spinal-cord-injured mice, with different senolytic drugs, improves locomotor, sensory, and bladder functions. This functional recovery is associated with improved myelin sparing, reduced fibrotic scar, and attenuated inflammation, which correlate with a decreased secretion of pro-fibrotic and pro-inflammatory factors. Targeting SCs is a promising therapeutic strategy not only for spinal cord injuries but potentially for other organs that lack regenerative competence.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNParamos-de-Carvalho, DiogoMartins, IsauraCristóvão, Ana MargaridaDias, Ana FilipaNeves-Silva, DalilaPereira, TelmoChapela, DianaFarinho, AnaJacinto, AntónioSaúde, Leonor2021-07-21T22:19:43Z2021-07-062021-07-06T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/121435eng2211-1247PURE: 32498323https://doi.org/10.1016/j.celrep.2021.109334info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:03:44Zoai:run.unl.pt:10362/121435Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:44:36.397843Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Targeting senescent cells improves functional recovery after spinal cord injury |
title |
Targeting senescent cells improves functional recovery after spinal cord injury |
spellingShingle |
Targeting senescent cells improves functional recovery after spinal cord injury Paramos-de-Carvalho, Diogo Biochemistry, Genetics and Molecular Biology(all) |
title_short |
Targeting senescent cells improves functional recovery after spinal cord injury |
title_full |
Targeting senescent cells improves functional recovery after spinal cord injury |
title_fullStr |
Targeting senescent cells improves functional recovery after spinal cord injury |
title_full_unstemmed |
Targeting senescent cells improves functional recovery after spinal cord injury |
title_sort |
Targeting senescent cells improves functional recovery after spinal cord injury |
author |
Paramos-de-Carvalho, Diogo |
author_facet |
Paramos-de-Carvalho, Diogo Martins, Isaura Cristóvão, Ana Margarida Dias, Ana Filipa Neves-Silva, Dalila Pereira, Telmo Chapela, Diana Farinho, Ana Jacinto, António Saúde, Leonor |
author_role |
author |
author2 |
Martins, Isaura Cristóvão, Ana Margarida Dias, Ana Filipa Neves-Silva, Dalila Pereira, Telmo Chapela, Diana Farinho, Ana Jacinto, António Saúde, Leonor |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
dc.contributor.author.fl_str_mv |
Paramos-de-Carvalho, Diogo Martins, Isaura Cristóvão, Ana Margarida Dias, Ana Filipa Neves-Silva, Dalila Pereira, Telmo Chapela, Diana Farinho, Ana Jacinto, António Saúde, Leonor |
dc.subject.por.fl_str_mv |
Biochemistry, Genetics and Molecular Biology(all) |
topic |
Biochemistry, Genetics and Molecular Biology(all) |
description |
Funding Information: We are grateful to A. Nascimento, A. Temudo, and J. Rino from the Bioimaging Unit for all of their precious advice. We thank the support given by the Fish and Rodent Facilities and the Histology and Comparative Pathology Laboratory, A. Ribeiro and C. de Sena-Tomás for critical reading of the manuscript, and M. Rebocho-da-Costa for help with the graphical abstract. D.P.d.C. was supported by a FCT PhD fellowship ( PD/BD/105770/2014 ). I.M. was supported by a FCT post-doctoral fellowship ( SFRH/BPD/118051/2016 ). A.M.C. was supported by a FCT fellowship ( PTDC/BOM-MED/3295/2014 ). A.F.D. was supported by CONGENTO LISBOA-01-0145-FEDER-022170 , co-financed by FCT (Portugal) and Lisboa2020 , under the PORTUGAL2020 agreement ( European Regional Development Fund ). D.N.-S. was supported by a FCT PhD fellowship ( SFRH/BD/138636/2018 ). D.C. was supported by a FCT PhD fellowship ( PD/BD/114179/2016 ). L.S. was supported by a FCT IF contract. The project leading to these results has received funding from a FCT grant ( PTDC/MED-NEU/30428/2017 ) and “la Caixa” Banking Foundation and FCT , I.P., under project code HR18-00187 . Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-07-21T22:19:43Z 2021-07-06 2021-07-06T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/121435 |
url |
http://hdl.handle.net/10362/121435 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2211-1247 PURE: 32498323 https://doi.org/10.1016/j.celrep.2021.109334 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
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