Searching for rejuvenating and neuroregenerative strategies in the senescent killifish visual system

Due to the rise in life expectancy, neurodegenerative diseases associated with aging, such as Alzheimer's and Parkinson's disease but also glaucoma, show an increasing prevalence. As neuroregenerative capacities are absent in the adult mammalian central nervous system (CNS), brain trauma and neurodegeneration are often permanent and severely diminish life quality of these (older) patients, which immediately highlights a growing socio-economic problem. Although recent intensive research efforts focus on the mechanisms that trigger repair in the mammalian brain, the effect of aging on neuroregenerative processes remains largely unstudied. In contrast to mammals, the short-lived turquoise killifish, Nothobranchius furzeri, has a remarkable regenerative ability in the adult CNS. Moreover, its compressed lifespan is associated with rapid growth, early sexual maturation, and typical signs of aging at the molecular, cellular and physiological level. Indeed, despite showing substantial growth during adult life, these fish do age and many of the 'hallmarks of aging' have been shown to occur in N. furzeri. In this project, aging processes and the effect of aging on regenerative abilities will be studied in the killifish retinotectal system, a well-known part of the CNS. We will establish an optic nerve injury model to enable the identification and screening of regenerative molecules in an aging environment. Using a combination of state-of-the-art technologies, we envision unveiling new targets for future development of therapeutic strategies in the senescent mammalian CNS. Thus, besides being an excellent model for studying CNS aging processes, we put the killifish forward as being particularly suited to identify potential targets for novel reparative strategies in the diseased CNS.

Publication year:2021

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