A recent study has found that the African turquoise killifish, known for its high regenerative abilities, loses this capacity as it ages, adopting a limited form of mammalian regeneration. Researchers used a proteomic strategy (analysing the proteins) to understand the pathways that are affected by ageing, highlighting cellular senescence as a potential inhibitor of successful neurorepair. By applying a senolytic cocktail of Dasatinib and Quercetin (D + Q), they managed to reduce chronic senescent cells in the aged killifish central nervous system (CNS) and reboot neurogenic output, providing a potential therapy to revive neurogenic potential in an aged or diseased CNS.
- Cellular senescence: Cellular senescence (ageing at the cellular level) was identified as a significant factor that potentially inhibits successful neurorepair (repair of nerve cells and structures)
- Senolytic cocktail: A combination of two drugs, Dasatinib and Quercetin (D + Q), was used to test the clearance of chronic senescent cells from the aged killifish CNS
- Results from D + Q treatment: The treatment showed that the entire aged killifish telencephalon (part of the brain) holds a very high senescent cell burden, which could be reduced by a short-term, late-onset D + Q treatment
- Impact on neurogenesis: After traumatic brain injury, reactive proliferation of non-glial progenitors increased substantially, leading to restorative neurogenesis (creation of new nerve cells)
- Potential therapy insight: The findings provide a cellular mechanism for age-related regeneration resilience and a proof-of-concept of a potential therapy to revive the neurogenic potential in an already aged or diseased CNS
Reference: Van houcke, J., Mariën, V., Zandecki, C. et al. A short dasatinib and quercetin treatment is sufficient to reinstate potent adult neuroregenesis in the aged killifish. npj Regen Med 8, 31 (2023). https://doi.org/10.1038/s41536-023-00304-4