Autor(es): Paramos-de-Carvalho, Diogo ; Martins, Isaura ; Cristóvão, Ana Margarida ; Dias, Ana Filipa ; Neves-Silva, Dalila ; Pereira, Telmo ; Chapela, Diana ; Farinho, Ana ; Jacinto, Antonio ; Saúde, Leonor
Data: 2021
Identificador Persistente: http://hdl.handle.net/10362/121435
Origem: Repositório Institucional da UNL
Assunto(s): Biochemistry, 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.
