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

项目描述（申请人提供）：本项目旨在通过研究长寿秀丽隐杆线虫daf-2突变体来增强对衰老过程的理解。将开发一种数据独立采集质谱方案，以实现对C. elegans蛋白质组在整个衰老过程中。为此，将编写软件以解卷积源自多种前体裂解的MS/MS谱。C.具有生殖系突变以避免后代发育的秀丽线虫将同步生长。待培养的菌株包括glp-4菌株、glp-4; daf-2突变菌株和daf-16 glp-4; daf-2突变菌株。这些菌株的蛋白质谱将随着时间的推移进行分析，以揭示衰老途径的新成分，并生成“分子年龄”的度量。将确定“分子年龄”和实足年龄之间的关系。 公共卫生相关性：该项目将提供对衰老过程的深入了解，并可能提供在人类中观察到的热量限制与长寿之间的关系。该项目将试图揭示一种线虫（秀丽隐杆线虫）使其寿命延长一倍的机制。对这种机制的理解可以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.