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.

This paper reports a phylogeny of the African killifishes (Genus Nothobranchius, Order Cyprinodontiformes) informed by five genetic markers (three nuclear, two mitochondrial) of 80 taxa (seven undescribed and 73 of the 92 recognized species). These short-lived annual fishes occupy seasonally wet habitats in central and eastern Africa, and their distribution coincides largely with the East African Rift System (EARS). The fossil dates of sister clades used to constrain a chronometric tree of all sampled Nothobranchius recovered the origin of the genus at ~13.27 Mya. It was followed by the radiations of six principal clades through the Neogene. An ancestral area estimation tested competing biogeographical hypotheses to constrain the ancestral origin of the genus to the Nilo-Sudan Ecoregion, which seeded a mid-Miocene dispersal event into the Coastal ecoregion, followed closely (~10 Mya) by dispersals southward across the Mozambique coastal plain into the Limpopo Ecoregion. Extending westwards across the Tanzanian plateau, a pulse of radiations through the Pliocene were associated with dispersals and fragmentation of wetlands across the Kalahari and Uganda Ecoregions. We interpret this congruence of drainage rearrangements with dispersals and cladogenic events of Nothobranchius to reflect congruent responses to recurrent uplift and rifting. The coevolution of these freshwater fishes and wetlands is attributed to ultimate control by tectonics, as the EARS extended southwards during the Neogene. Geobiological consilience of the combined evidence supports a tectonic hypothesis for the evolution of Nothobranchius.

Le système cardio-respiratoire joue un rôle prépondérant au sein d’un organisme, en permettant notamment l’apport et la distribution du dioxygène et des nutriments à l’ensemble des cellules. Mieux comprendre les modifications du système cardio-respiratoire au cours de la vie est donc un élément central dans l’évaluation de la capacité de l’organisme à répondre à ses différents besoins énergétiques, ainsi que dans la compréhension du phénomène de mortalité naturelle liée à la sénescence. Cette étude a été réalisée sur un vertébré à durée de vie extrêmement courte (~6 mois), le poisson Nothobranchius furzeri. La température, en plus d’être considérée comme l’un des principaux facteurs environnementaux susceptibles d’influencer la physiologie des téléostéens, est connue pour son effet régulateur sur la longévité. Ainsi, les individus étaient acclimatés à deux températures, 26 °C considérée comme la température optimale chez cette espèce, et une température réduite de 22 °C. Au niveau individuel, les réponses biologiques ont été explorées au travers des performances physiologiques comme mesure indirecte de la fitness : la capacité métabolique aérobie (AS), la croissance, les performances de reproduction, de locomotion et de digestion. A l’échelle sub-individuelle, les mécanismes de régulation de la fonction cardiaque ont été examinés via une étude morpho-fonctionnelle des cardiomyocytes. Les résultats mettent en évidence la présence au cours de la vie de deux phases bien distinctes délimitées par un âge optimal : (1) une première phase d’élévation de l’AS des stades juvénile à adulte ; suivie (2) d’une seconde phase, synonyme de déclin de l’AS, des indicateurs cardiaques et des niveaux d’activités ciblés, associés probablement à l’entrée en sénescence. Une réduction de température accroit la longévité, et retarde les effets néfastes du vieillissement sur l’AS, et les performances cardiaques. Cette étude contribuera à établir une vision globale des effets du vieillissement sur la fonction cardio-respiratoire et à mieux comprendre les mécanismes mis en jeu lors d’un allongement de la longévité par une réduction de la température. / Cardio-respiratory system plays a key role in an organism by delivering oxygen and nutrients towards the cells. Exploring its age-dependant changes is therefore a corner stone for assessing the organism capacity to meet its energetic needs along its life cycle, and for the understanding of mechanisms involved in the mortality due to aging process. This study was realized in a vertebrate with an extremely short lifespan (~6 months), the fish Nothobranchius furzeri. Temperature is an external factor that regulates longevity. Here, fish were acclimatized at two temperatures, 26 °C considered as the optimal temperature for this species, and 22 °C. Biological responses of fish were evaluated at individual level through the assessment of aerobic metabolic scope (AS), growth, reproduction, locomotion and digestion, which are considered to be relevant indirect measurement of fitness. Furthermore, mechanisms involved in the cardiac function regulation were explored through a morpho-functional study of cardiomyocytes. Along the individual life cycle, two phases were emphasized: 1) the first corresponds to AS elevation from the juvenile to the adult stages, following by 2) a second phase reflecting the entrance in the senescent stage, characterized by the decline in AS, cardiac performances and in activity level. A temperature reduction increases the individual longevity and slows-down deleterious effect of aging on both AS and cardiac function. This study will contribute to provide a global vision of senescent effects on cardio-respiratory system, and a better understanding of the mechanisms involved in temperature-dependent increase in longevity.

I used annual killifish Nothobranchius orthonotus to investigate two separate questions related to behavioural aspects of their life history. The first study focused on spatial cognitive ability of two N. orthonotus populations that originated from temporary pools that varied in their expected duration due to differences in annual precipitation patterns (dry and humid region). Test of cognition was based on the ability to learn to find food in a dichotomous test. It was assumed that learning ability differs between populations when tested in young and old age along with their difference in captive lifespan. Additionally, association between cognitive ability and other life history traits was tested. It was found that: (1) there was no difference in the ability to learn spatial task between populations; (2) both populations had similar lifespan with no cognitive decay in older age, and older fish from dry region population had committed even less errors in the learning task than they did as young fish; (3) fish were able to effectively learn the task but (4) solitary fish had lower learning ability than group-reared fish; (5) longer- living fish were quicker learners; (6) high resting metabolic rate was associated with more effective learning; (7) hesitant fish found the food reward in learning task...