High-throughput multi-modal analysis of natural variation in C. elegans healthspan

项目总结 衰老的变异中有很大一部分可以用遗传学来解释，但人们对什么原因知之甚少 这些遗传因素以及它们是如何调节健康衰老的。我们对此的许多基本理解 调节衰老的机制，包括胰岛素信号和蛋白平衡途径，来自这项研究 模式线虫秀丽线虫的线虫。几乎所有的线虫衰老研究都使用一个实验室- 适应菌株，与自然变异关系不大。在这个项目中，我们的目标是建立线虫作为一种 衰老的自然变异模型。首先，我们将开发一个多模式自动化医疗系统 基于先前开发的‘WorMotel’微型制造多井成像平台的分析。第二，我们 将对16个基因分化的野生线虫菌株进行纵向测试，以确定特征 与健康寿命下降相关。我们的结果将为全面的机理分析奠定基础。 衰老过程中自然变异的基因。将高通量健康寿命分析与 数量遗传学方法将在描述复杂的遗传原因方面特别强大 健康跨度表型，提供了对后生动物衰老中自然变异的第一个机械理解。

PROJECT SUMMARY A substantial fraction of the variation in aging can be explained by genetics, but little is known about what these genetic factors are and how they modulate healthy aging. Much of our fundamental understanding of mechanisms that modulate aging, including insulin signaling and proteostasis pathways, come from the study of the model nematode Caenorhabditis elegans. Nearly all C. elegans aging studies use a single laboratory- adapted strain with little connection to natural variation. In this project we aim to establish C. elegans as a model for natural variation in aging. First we will develop a system for multi-modal automated healthspan assays based on a previously developed `WorMotel' microfabricated multi-well imaging platform. Second, we will carry out longitudinal assays on 16 genotypically diverged wild-isolate C. elegans strains to determine traits correlated with healthspan decline. Our results will set the stage for comprehensive mechanistic analysis of genes underlying natural variation in aging. The combination of high-throughput healthspan analysis and quantitative genetics methods will be particularly powerful for delineating genetic causes of a complex healthspan phenotype, providing the first mechanistic understanding of natural variation in metazoan aging.