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.
02 /Specification & Classification
Click any tag to browse matching papers- Citations
- 74
- FWCI
- 7.99
- Field percentile
- top 1%
- Organism
- Research Focus
- Approach
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Early migration of precursor neurons initiates cellular and functional regeneration after spinal cord injury in zebrafish.
Celia Vandestadt, Gilles Claude Vanwalleghem, … Jan Kaslin·Developmental CellPeer-reviewed·Aug 1, 2021
- Elevated phagocytic capacity directs innate spinal cord repair
Dana Klatt Shaw, Vishnu Muraleedharan Saraswathy, … Mayssa H. Mokalled·Cell ReportsPeer-reviewed·Jun 1, 2026
- Microglia limit lesion expansion and promote functional recovery after spinal cord injury in mice
Faith H. Brennan, Jodie C.E. Hall, … Phillip G. Popovich·bioRxiv·Sep 6, 2018
- Functional Trajectories during innate spinal cord repair
Nicholas O. Jensen, Brooke Burris, … Mayssa H. Mokalled·Frontiers in Molecular NeurosciencePeer-reviewed·Jul 10, 2023
- New functional vessels form after spinal cord injury in zebrafish
Ana Ribeiro, Mariana Rebocho da Costa, … Leonor Saúde·bioRxiv·Jun 9, 2022
- Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair.
Vishnu Muraleedharan Saraswathy, Lili Zhou, Mayssa H. Mokalled·Nature CommunicationsPeer-reviewed·Aug 15, 2024