Developing the Zebrafish as an animal model for aging

申请的重点是主题：老龄化的动物模型，隶属于国家老龄研究所增强资源支持高质量研究的优先领域。斑马鱼是衰老研究的一个相对较新的模型，部分原因是斑马鱼只是在最近五到十年才被广泛用于任何类型的研究。最近斑马鱼作为一种被广泛研究的物种的出现，现在为利用这一模型进行衰老研究提供了机会。这项实验设计旨在生成衰老和卡路里限制的斑马鱼的基因表达谱，这与目前公认的衰老模型小鼠相似。卡路里限制(CR)是唯一已知的干预措施，可以减缓年龄相关疾病的发生率，并延长包括啮齿类动物和斑马鱼在内的各种生物的寿命。大规模微阵列已经成为分析基因表达的有力工具。这种方法已经被用于研究小鼠一些组织的衰老和卡路里限制。我们将分析短期热量限制和老化过程中斑马鱼大脑、心脏和骨骼肌中的基因表达。随后，我们将把我们的基因表达谱与最近文献中报道的具有相似寿命的动物模型小鼠的基因表达谱进行比较。虽然我们不期望动物之间的结果是相同的，但由于物种特定的衰老过程的差异和方案的不同，我们确实希望看到从根本上适用于衰老过程的途径展示至少在方向上一致的变化 两个模式系统之间的变化。两个模型之间的比较将为衰老过程及其卡路里限制的抑制提供有价值的见解。

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.