A Short Dasatinib and Quercetin Treatment is Sufficient to Reinstate Potent Adult Neuroregenesis in the Aged Killifish

Overview

Journal NPJ Regen Med

Date 2023 Jun 16

PMID 37328477

Authors

Jolien Van Houcke

Valerie Marien

Caroline Zandecki

Rajagopal Ayana

Elise Pepermans

Kurt Boonen

Eve Seuntjens

Geert Baggerman

Lutgarde Arckens

Affiliations

Soon will be listed here.

Abstract

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.

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