Targeting senescent cells improves functional recovery after spinal cord injury

Diogo Paramos-de-Carvalho, Isaura Martins, Ana Margarida Cristóvão, Ana Filipa Dias, Dalila Neves-Silva, Telmo Pereira, Diana Chapela, Ana Farinho, António Jacinto, Leonor Saúde

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Abstract

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.

Original languageEnglish
Article number109334
JournalCell Reports
Volume36
Issue number1
DOIs
Publication statusPublished - 6 Jul 2021

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