PUBLICATION
Targeting senescent cells improves functional recovery after spinal cord injury
- 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.
- ID
- ZDB-PUB-210708-9
- Date
- 2021
- Source
- Cell Reports 36: 109334 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- White Matter/drug effects
- White Matter/pathology
- White Matter/physiopathology
- Mice, Inbred C57BL
- Senotherapeutics/administration & dosage
- Senotherapeutics/pharmacology
- Cell Count
- Macrophages/drug effects
- Macrophages/pathology
- Sensation/drug effects
- Spinal Cord/drug effects
- Spinal Cord/pathology
- Spinal Cord/physiopathology
- Zebrafish
- Aniline Compounds/administration & dosage
- Aniline Compounds/pharmacology
- Down-Regulation/drug effects
- Disease Models, Animal
- Cicatrix/pathology
- Myelin Sheath/metabolism
- Spinal Cord Injuries/pathology*
- Spinal Cord Injuries/physiopathology*
- Neurons/drug effects
- Neurons/pathology
- Animals
- Fibrosis
- Sulfonamides/administration & dosage
- Sulfonamides/pharmacology
- Recovery of Function*/drug effects
- Urinary Bladder/drug effects
- Urinary Bladder/pathology
- Urinary Bladder/physiopathology
- Inflammation Mediators/metabolism
- Motor Activity/drug effects
- Cellular Senescence*/drug effects
- PubMed
- 34233184 Full text @ Cell Rep.
Citation
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. (2021) Targeting senescent cells improves functional recovery after spinal cord injury. Cell Reports. 36:109334.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping