Developing the Zebrafish as an animal model for aging

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The focus of the application addresses the topic: Animal Models of Aging, under the National Institute on Aging's priority area of Enhancing Resources to Support High Quality Research. Zebrafish is a relatively new model for aging research, in part because it has been only in the last five to ten years that zebrafish have been used extensively for any type of research. The recent emergence of the zebrafish as a widely studied species now provides an opportunity to exploit this model for aging research. The experimental design is structured to generate gene expression profiles in aging and caloric restricted zebrafish that approximates a currently accepted aging model, the mouse. Caloric restriction (CR) is the only known intervention shown to slow incidence of age-related diseases and extend lifespan in a wide variety of organisms, including rodents and zebrafish. Large-scale microarrays have emerged as a powerful tool to profile gene expression. This approach has been used to study aging and caloric restriction in a number of tissues in the mouse. We will profile gene expression in brain, heart and skeletal muscle from zebrafish subject to short-term caloric restriction, and during aging. Subsequently, we will compare our gene expression profiles to those reported recently in the literature for an animal model having a similar life span, the mouse. While we do not expect the results between animals to be identical, due to the variations in species specific process of aging and the differences in protocols, we do expect to see pathways that are fundamentally applicable to the aging process demonstrate changes that are at least consistent in the direction of change between the two model systems. Comparisons between the two models should provide valuable insights into the aging process and its inhibition by caloric restriction.