A short dasatinib and quercetin treatment is sufficient to reinstate potent adult neuroregenesis in the aged killifish.

Autor: Van Houcke J; Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology, KU Leuven, 3000, Leuven, Belgium., Mariën V; Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology, KU Leuven, 3000, Leuven, Belgium., Zandecki C; Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology, KU Leuven, 3000, Leuven, Belgium.; Laboratory of Developmental Neurobiology, Department of Biology, KU Leuven, 3000, Leuven, Belgium., Ayana R; Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology, KU Leuven, 3000, Leuven, Belgium.; Laboratory of Developmental Neurobiology, Department of Biology, KU Leuven, 3000, Leuven, Belgium., Pepermans E; Centre for Proteomics, University of Antwerp, 2020, Antwerpen, Belgium., Boonen K; Centre for Proteomics, University of Antwerp, 2020, Antwerpen, Belgium.; Health Unit, VITO, 2400, Mol, Belgium., Seuntjens E; Laboratory of Developmental Neurobiology, Department of Biology, KU Leuven, 3000, Leuven, Belgium.; KU Leuven Brain Institute, KU Leuven, 3000, Leuven, Belgium., Baggerman G; Centre for Proteomics, University of Antwerp, 2020, Antwerpen, Belgium.; Health Unit, VITO, 2400, Mol, Belgium., Arckens L; Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology, KU Leuven, 3000, Leuven, Belgium. lut.arckens@kuleuven.be.; KU Leuven Brain Institute, KU Leuven, 3000, Leuven, Belgium. lut.arckens@kuleuven.be.
Jazyk: angličtina
Zdroj: NPJ Regenerative medicine [NPJ Regen Med] 2023 Jun 16; Vol. 8 (1), pp. 31. Date of Electronic Publication: 2023 Jun 16.
DOI: 10.1038/s41536-023-00304-4
Abstrakt: The young African turquoise killifish has a high regenerative capacity, but loses it with advancing age, adopting several aspects of the limited form of mammalian regeneration. We deployed a proteomic strategy to identify pathways that underpin the loss of regenerative power caused by aging. Cellular senescence stood out as a potential brake on successful neurorepair. We applied the senolytic cocktail Dasatinib and Quercetin (D + Q) to test clearance of chronic senescent cells from the aged killifish central nervous system (CNS) as well as rebooting the neurogenic output. Our results show that the entire aged killifish telencephalon holds a very high senescent cell burden, including the parenchyma and the neurogenic niches, which could be diminished by a short-term, late-onset D + Q treatment. Reactive proliferation of non-glial progenitors increased substantially and lead to restorative neurogenesis after traumatic brain injury. Our results 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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