Cited by 74Spinal Cord Injury ResearchTelomeres, Telomerase, and SenescenceNerve injury and regeneration

Targeting senescent cells improves functional recovery after spinal cord injury

Open access
Paramos-de-Carvalho, Diogo, Martins, Isaura, Cristóvão, Ana Margarida, Dias, Ana Filipa, Neves-Silva, Dalila, Pereira, Telmo, Chapela, Diana, Farinho, Ana +2 more·2021·Cell Reports

Published version of a preprint

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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Crossref · 10.1016/j.celrep.2021.109334

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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
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
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

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