Identification of Biomarkers in Zebrafish Aging

斑马鱼衰老生物标志物的鉴定

基本信息

批准号：
6897474
负责人：
SHUJI KISHI
金额：
$ 8.55万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-06-01 至 2006-05-31
项目状态：
已结题

项目摘要

The zebrafish (Danio rerio) has proved to be an outstanding animal model system for genetic studies to explore vertebrate diseases as well as development. However, most zebrafish researchers evaluate their mutant animals at the embryonic and larval stages. Thus, mutations which mediate the effects of late-age onset diseases or dysfunctions have not been identified. More primitive model organisms such as Caenorhabditis elegans and Drosophila melanogaster have already been utilized quite successfully for genetic studies of aging, which have identified key evolutionarily conserved genes associated with the aging process. However, these invertebrate models cannot sufficiently identify critical longevity genes that are unique to vertebrates. Therefore it seems obvious that if the zebrafish system, with its the well-established advantages of forward genetics and recently improved reverse genetic technology, could be adapted to study aging, it would present an unparalleled opportunity to advance aging research. A number of theories to explain aging in mammals have been advanced over the years. Theories currently in vogue suggest that aging is the regulated by oxidative or genotoxic stress, telomere metabolism, regulation of caloric restriction and control of metabolic energy rate. Notably these theories are not mutually exclusive. However, compared to mammals, the aging process of zebrafish has gone almost unstudied. We propose to lay a strong foundation for aging studies in the zebrafish. First and foremost, we will perform an intensive search for biological and biochemical aging markers in zebrafish over the course of its entire lifespan (Aim 1). We will then begin to examine the effects treatments thought to regulate aging such as genotoxic stress by ionizing radiation or oxidative stress by hydrogen peroxide on the aging process of zebrafish using the most robust of our markers (Aim 2). These studies should prepare the way for later forward and reverse genetic studies where we will seek premature aging phenotypes or phenotypes resistant to aging and senescence in zebrafish.

斑马鱼（Danio Rerio）已被证明是一种杰出的遗传研究动物模型系统，用于探索脊椎动物疾病和发育。但是，大多数斑马鱼研究人员在胚胎和幼虫阶段评估其突变动物。因此，尚未鉴定出介导晚期发作疾病或功能障碍的影响的突变。诸如秀丽隐杆线虫和果蝇果蝇等更原始的模型生物已经非常成功地用于衰老的遗传研究，这些研究已经确定了与衰老过程相关的关键进化基因。但是，这些无脊椎动物模型无法充分识别关键的寿命基因脊椎动物独有。因此，很明显，如果斑马鱼系统具有远期遗传学的良好优势和最近改进的反向遗传技术，可以适应研究衰老，则它将提供无与伦比的机会来提高衰老研究。多年来，许多解释哺乳动物衰老的理论已经提高。理论目前的流行表明，衰老是受氧化或遗传毒性应激，端粒代谢，热量限制的调节和代谢能率的控制的调节。值得注意的是，这些理论不是相互排斥的。但是，与哺乳动物相比，斑马鱼的衰老过程几乎没有被研究。我们建议在斑马鱼中为衰老研究奠定坚实的基础。首先，我们将在整个生命周期内对斑马鱼中的生物学和生化衰老标记进行深入搜索（AIM 1）。然后，我们将开始检查被认为调节衰老的效应治疗方法，例如通过我们最强大的标记物电离辐射或过氧化氢的氧化应激对斑马鱼的衰老过程（AIM 2）。这些研究应该为以后的方式做准备向前和逆转遗传研究，我们将寻求斑马鱼中对衰老和衰老的耐老化表型或表型的过早衰老。