Killifish switch towards mammalian-like regeneration upon aging

Abstract

In our aging society, the prevalence of brain trauma and age-related neurodisorders, in which neurons are damaged and/or lost, has been increasing. Unfortunate-ly, spontaneous recovery from these conditions is not occurring in humans, as both neuron-intrinsic and -extrinsic factors hinder regeneration in the adult mammalian central nervous system (CNS). One way to discover novel targets to promote CNS repair, is to use model organisms that are capable of restoring damage in their adult CNS. Unlike mammals, several teleost species retain their neuroregenerative ability after birth, and can successfully replace lost neurons and regrow severed axons throughout adulthood. This has resulted in fish models becoming increasingly popular to study injury-induced CNS recovery, and to help deciphering the cellular and molecular mechanisms that are required for functional circuit restoration in the adult mammalian brain. Indeed, despite the difference in repair capacity between fish and mammals, many molecules and processes that regulate neuroregeneration are conserved within vertebrate species, and findings obtained in fish are considered transferable to humans [1]. How aging impacts the fish’s ability to functionally recover from CNS damage, however, has only been limitedly studied up till now.