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

时间过程蛋白质组学揭示线虫衰老的机制和本质

• 批准号: 7911388
• 负责人: Jarrett David Egertson
• 金额: $ 3.98万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2013-10-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7911388
• 关键词: Age; Aging; Aging-Related Process; Caenorhabditis elegans; Caloric Restriction; Computer software; Data; Development; Germ-Line Mutation; Human; Life; Longevity; Mass Spectrum Analysis; Methods; Metric; Molecular; Nature; Nematoda; Pathway interactions; Proteome; Proteomics; Scheme; Time; Writing; insight; mutant; offspring; protein profiling; public health relevance

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.

描述（由申请人提供）：本项目旨在通过研究长寿的秀丽隐杆线虫daf-2突变体，提高对衰老过程的认识。将开发一种数据独立采集质谱方案，以便在整个衰老过程中对秀丽隐杆线虫蛋白质组进行高灵敏度、高动态范围、可量化的分析。为此，将编写软件来反卷积来自多个前体碎片的MS/MS谱。秀丽隐杆线虫，通过种系突变来避免后代的发育，将同步生长。将要培养的菌株包括glp-4菌株，glp-4；Daf-2突变株和daf-16 glp-4；Daf-2突变株。随着时间的推移，这些菌株的蛋白质谱将被分析，以揭示衰老途径的新成分，并产生“分子年龄”的度量。“分子年龄”和实足年龄之间的关系将被确定。