Targeting senescent cells improves functional recovery after spinal cord injury

Bibliographic Details
Main Author: Paramos-de-Carvalho, Diogo
Publication Date: 2021
Other Authors: Martins, Isaura, Cristóvão, Ana Margarida, Dias, Ana Filipa, Silva, Dalila, Pereira, Telmo, Chapela Pires, Diana, Farinho, Ana, Jacinto, António, Saúde, Leonor
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/49465
Summary: © The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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spelling Targeting senescent cells improves functional recovery after spinal cord injury© The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)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.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.ElsevierRepositório da Universidade de LisboaParamos-de-Carvalho, DiogoMartins, IsauraCristóvão, Ana MargaridaDias, Ana FilipaSilva, DalilaPereira, TelmoChapela Pires, DianaFarinho, AnaJacinto, AntónioSaúde, Leonor2021-09-08T14:06:17Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49465engCell Rep. 2021 Jul 6;36(1):109334.2211-124710.1016/j.celrep.2021.109334info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:36:56Zoai:repositorio.ulisboa.pt:10451/49465Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:17:04.126243Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
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
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
Silva, Dalila
Pereira, Telmo
Chapela Pires, Diana
Farinho, Ana
Jacinto, António
Saúde, Leonor
author_role author
author2 Martins, Isaura
Cristóvão, Ana Margarida
Dias, Ana Filipa
Silva, Dalila
Pereira, Telmo
Chapela Pires, Diana
Farinho, Ana
Jacinto, António
Saúde, Leonor
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Paramos-de-Carvalho, Diogo
Martins, Isaura
Cristóvão, Ana Margarida
Dias, Ana Filipa
Silva, Dalila
Pereira, Telmo
Chapela Pires, Diana
Farinho, Ana
Jacinto, António
Saúde, Leonor
description © The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
publishDate 2021
dc.date.none.fl_str_mv 2021-09-08T14:06:17Z
2021
2021-01-01T00:00:00Z
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/10451/49465
url http://hdl.handle.net/10451/49465
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Cell Rep. 2021 Jul 6;36(1):109334.
2211-1247
10.1016/j.celrep.2021.109334
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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