Targeting senescent cells improves functional recovery after spinal cord injury
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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.
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- Authors
- Paramos-de-Carvalho, D., Martins, I., Cristóvão, A. M., Dias, A. F., Neves-Silva, D., Pereira, T., Chapela, D., Farinho, A., Jacinto, A., & Saúde, L.
- Affiliations
- University of Lisbon (PT)
- Universidade Nova de Lisboa (PT)
- Corresponding author
- Saúde, Leonor
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 36
- Issue
- 1
- Pages
- 109334
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W3182661487
- Cited by
- 74
- References
- 109
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 16 · 2023: 15 · 2022: 11 · 2021: 6
- FWCI
- 8.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Funders
- European Regional Development Fund (SFRH/BD/138636/2018, PTDC/MED-NEU/30428/2017, PD/BD/114179/2016)
- Fundação para a Ciência e a Tecnologia (PTDC/MED-NEU/30428/2017, PTDC/BOM-MED/3295/2014, PD/BD/105770/2014, SFRH/BPD/118051/2016)
- Universidade Nova de Lisboa
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- senescent cells, senolytics, spinal cord injury, functional recovery, tissue regeneration, fibrotic scar, neuroinflammation, locomotor recovery, sensory recovery, bladder function, zebrafish regeneration
- MeSH terms
- Senotherapeutics, Aniline Compounds, Animals, Urinary Bladder, Cell Count, Cicatrix, Disease Models, Animal, Fibrosis, Macrophages, Mice, Inbred C57BL, Motor Activity, Myelin Sheath, Neurons, Sensation, Spinal Cord, Spinal Cord Injuries, Sulfonamides, Zebrafish, Down-Regulation, Cellular Senescence, Inflammation Mediators, Recovery of Function, Mice, White Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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