PROTEOMICS OF LIFE SPAN EXTENSION IN C ELEGANS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 梭秀丽线虫是一种非常短命的多细胞生物体，在最佳实验室条件下的寿命仅为2-3周。 如此短的寿命，加上积累了大量关于这种生物体的生理学、形态学和遗传学的知识，使其成为研究衰老基本机制的最方便的模型之一。 已经表明，野生型C. elegans可以通过许多看似独立的方式进行大幅扩展。 例如，它可以通过饮食限制、通过Ins/IGF信号传导途径的突变或通过线粒体功能的下调而延长高达数倍。 然而，尽管积累了生理和主要遗传数据，但衰老现象和寿命延长背后的分子机制尚未完全概述。 在这个NCRR合作提案中，我们希望超越传统上用于研究C的方法。elegans老化，并采取了详细的蛋白质组研究。 在这里，在一个试点研究中，我们建议看看蛋白质组的变化，随着年龄的正常生活的蠕虫，长寿的突变蠕虫和饮食限制蠕虫。 我们的目标是找到影响寿命的常见下游蛋白质或某些过程（如特定蛋白质降解途径）的常见印记。 这个新的替代品看C。从蛋白质组学的角度对线虫衰老过程的研究可能会为未来的研究提供新的途径，而不会受到现有衰老假说的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The C. elegans nematode worm is a very short-living multicellular organism with a lifespan of only 2-3 weeks in optimal laboratory conditions. Such a short lifespan, in addition to accumulated wealth of knowledge about the physiology, morphology and genetics of this organism makes it one of the most convenient models to study the fundamental mechanisms of aging. It has been shown that the lifespan of wild-type C. elegans can be extended drastically in a number of seemingly independent ways. For example it can be extended up to several fold by dietary restriction, by mutation of the Ins/IGF signaling pathway, or by down-regulation of mitochondrial function. Nonetheless, despite the accumulated physiological and primarily genetic data, the molecular mechanisms behind the aging phenomenon and lifespan extension have not been fully outlined yet. In this NCRR collaborative proposal we want to move beyond approaches that have been traditionally used for studying C. elegans aging and take a detailed look at the proteome. Here, in a pilot study, we propose to look at the proteome changes over the age for normally lived worms, long-lived mutant worms and dietary restricted worms. Our goal is to find common downstream proteins or common imprints of certain processes (like specific protein degradation pathways) affecting longevity. This new alternative look at the C. elegans aging process from a proteomics perspective may yield new routes for future research that are not biased by existing aging hypotheses.