New models in which aging-related neurodegeneration more closely resembling the
combination of pathologies that develop in aging humans, are needed. The fish Nothobranchius,
which naturally develops such pathologies over the course of its short lifespan, is one such model.
This review compares the lifespans and pathologies of different Nothobranchius strains to those of
current vertebrate models of aging. Furthermore, existing data pertaining to neurodegeneration in
these fish is discussed in the context of their reported neuropathologies, along with open questions
related to mammalian chronopathologies. Specifically, the evidence for a Parkinson’s disease-like
pathology is discussed. Neurogenesis and age-related changes therein are discussed in the context
of siRNA and neurodegeneration. We also discuss changes in the expression of neuropeptide Y in
relation to the brain-gut axis and how these change with age. Age-related behavioral changes are
discussed, along with the assays used in their evaluation. Genetic discoveries are outlined and discussed
with a view on DJ-1/NRF2 signaling in N. furzeri, and insights gained from comparative
genomics and siRNA studies. Finally, research focus areas are highlighted, and a case is made for
the utility of these fish in the study of aging-related neurodegeneration, and to screen for environmental
risk factors of aging-related neuropathology.