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NeuroscienceCell Reports
Peer-reviewed journal article

Depletion of senescent cells improves functional recovery after spinal cord injury

Diogo Paramos-de-CarvalhoiD, Isaura MartinsiD, Ana Margarida Cristóvão, Ana F. DiasiD, Dalila Neves-SilvaiD, Telmo PereiraiD, Diana ChapelaiD, Ana FarinhoiD, António JacintoiD, Leonor SaúdeiD

Abstract

Persistent senescent cells (SCs) are known to underlie ageing-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. Here we show that two distinct senescence profiles are induced in the context of a spinal cord injury between the regenerating zebrafish and the non-regenerating mouse. While induced-SCs in the zebrafish are progressively cleared out, they accumulate over time in mice. Depletion of SCs in spinal cord injured mice, with different senolytic drugs, improved locomotor, sensory and bladder functions. This functional recovery is associated with improved myelin sparing, reduced fibrotic scar, attenuated inflammation and increased axonal growth. Targeting SCs is a promising therapeutic strategy not only for spinal cord injuries but potentially for other organs that lack regenerative competence.

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