PROTEOMICS OF LIFE SPAN EXTENSION IN C ELEGANS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 线虫是一种寿命非常短的多细胞生物体，在最佳实验室条件下寿命只有2-3周。如此短的寿命，加上积累的关于这种生物的生理、形态和遗传学的知识，使其成为研究衰老基本机制的最方便的模型之一。研究表明，野生型线虫的寿命可以通过许多看似独立的方式大幅延长。例如，通过限制饮食，通过INS/IGF信号通路的突变，或者通过下调线粒体功能，它可以扩展到几倍。然而，尽管积累了大量的生理和遗传数据，但衰老现象和寿命延长背后的分子机制尚未完全阐明。在NCRR的这项合作提案中，我们希望超越传统上用于研究线虫衰老的方法，并详细了解蛋白质组。在这里，在一项初步研究中，我们建议观察正常存活的蠕虫、长期存活的突变蠕虫和限制饮食的蠕虫的蛋白质组随年龄的变化。我们的目标是找到共同的下游蛋白或影响寿命的某些过程的共同印记(如特定的蛋白质降解途径)。从蛋白质组学的角度对线虫衰老过程进行这种新的替代研究，可能会为未来的研究提供新的路线，而不会受到现有衰老假说的偏见。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.