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Targeting senescent cells improves functional recovery after spinal cord injury

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Resumo: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.
Autores principais:Paramos-de-Carvalho, Diogo
Outros Autores:Martins, Isaura; Cristóvão, Ana Margarida; Dias, Ana Filipa; Neves-Silva, Dalila; Pereira, Telmo; Chapela, Diana; Farinho, Ana; Jacinto, António; Jacinto, Antonio; Saúde, Leonor
Assunto:General Biochemistry,Genetics and Molecular Biology
Ano:2021
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL

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