Time-Course Proteomics to Uncover the Mechanism and Nature of Aging in C. elegans

描述(申请人提供)：本项目旨在通过对长寿秀丽线虫daf-2突变体的研究，加强对衰老过程的了解。将开发一种独立于数据采集的质谱学方案，以实现对线虫蛋白质组在整个老化过程中的高灵敏度、高动态范围、可量化的分析。为此，将编写软件来解卷从多个前体的裂解得到的MS/MS光谱。带有胚系突变以避免后代发育的线虫将被同步生长。将要培养的菌株包括一株GLP-4菌株、一株GLP-4；daf-2突变株和一株daf-16 GLP-4；daf-2突变株。随着时间的推移，这些菌株的蛋白质图谱将被分析，以发现衰老途径的新成分，并产生一个衡量“分子年龄”的指标。“分子年龄”和年代年龄之间的关系将被确定。 公共卫生相关性：这个项目将提供对衰老过程的洞察，以及可能的卡路里限制和人类寿命之间的关系，这已经在人类身上观察到了。该项目将试图揭示使一种线虫(秀丽线虫)的寿命增加一倍的机制。对这一机制的理解可能会为研究和减缓人类衰老的新方法打开大门。

DESCRIPTION (provided by applicant): This project aims to enhance understanding of the aging process through the study of the long-lived Caenorhabditis elegans daf-2 mutant. A data-independent-acquisition mass spectrometry scheme will be developed to enable a high-sensitivity, high-dynamic range, quantifiable analysis of the C. elegans proteome throughout the aging process. To this end, software will be written to deconvolute MS/MS spectra derived from the fragmentation of multiple precursors. C. elegans, with a germ-line mutation to avoid development of offspring, will be synchronized and grown. Strains that will be grown include a glp-4 strain, a glp-4; daf-2 mutant strain, and a daf-16 glp-4; daf-2 mutant strain. The protein profile of these strains will be analyzed over time to uncover new components of the aging pathway as well as generate a metric for "molecular age". The relationship between "molecular age" and chronological age will be determined. PUBLIC HEALTH RELEVANCE: This project will provide insight into the aging process and possibly the relationship between caloric restriction and longevity which has been observed in humans. The project will attempt to uncover the mechanism that allows a species of nematode (Caenorhabditis elegans) to double its lifespan. An understanding of this mechanism could open the door to new methods of studying and slowing human aging.