Subcellular Analysis of Caenohabdibtis elegans Aging Models

秀丽隐杆线虫衰老模型的亚细胞分析

• 批准号: 8457310
• 负责人: EDGAR A ARRIAGA
• 金额: $ 6.2万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-02 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8457310
• 关键词: Aging; Aging-Related Process; Agreement; Animal Model; Animals; Caenorhabditis elegans; Cells; Collaborations; Complement; Complex; Disease; Electron Transport; Endoplasmic Reticulum; Environment; Fluorescence; Gene Targeting; Genetic; Health; Heat-Shock Response; Hormones; Human; Image; Insulin; Insulin-Like Growth Factor I; Intestines; Life; Longevity; Longevity Pathway; Maintenance; Mammals; Measurement; Measures; Micellar Electrokinetic Capillary Chromatography; Mitochondria; Mitotic; Modeling; Modification; Molecular; Nematoda; Neurons; Optics; Organ; Organelles; Organism; Pathway interactions; Peptides; Play; Positioning Attribute; Proteins; RNA Interference; Reactive Oxygen Species; Reading; Reporter; Reporting; Research; Resources; Role; Signal Transduction; Signaling Molecule; Soil; Sorting - Cell Movement; Span 20; Staging; Systems Biology; Technology; Testing; Tissues; Training; Work; age related; biological adaptation to stress; design; dietary restriction; experience; genetic manipulation; genome sequencing; interest; mutant; new technology; response; small molecule

DESCRIPTION (provided by applicant): The soil nematode Caenorhabditis elegans (C. elegans) is an excellent model organism for investigating the process of aging. The Dillin group uses long-lived C. elegans mutants that are deficient in the electron-transport chain (ETC). When the ETC deficiency occurs only in neurons, a mitochondria-specific stress response, known as the Unfolded Protein Response in mitochondria (UPRmt) is activated in the intestine, which in turn is required to sustain the mutant's extended lifespan. Long distance coordination between neurons and the intestine of the C. elegans mutants described above implies the existence of a signaling molecule (or molecules) that the Dillin group termed "mitokine". This F33 application explores the hypothesis: Mitochondrial ROS in neurons of ETC- deficient C. elegans are essential for mitokine signaling and the activation of the UPRmt response in the intestine of these mutants. During his sabbatical in the Dillin group, Dr. Arriaga proposes to use his bioanalytical expertise and experience in subcellular analysis of ROS to investigate the association that exists between ROS and mitokines. Dr. Dillin, who is a leader in the use of C. elegans for genetic and age-related studies, will provide a highly suited experimental and intellectual environment to complete the proposed work and train Dr. Arriaga in the use of C. elegans as a model organism of aging. The specific aims of the F33 application are: (1) Introduce Dr. Arriaga to C. elegans research during his sabbatical at the Dillin lab; (2) determine the role of mitochondrial ROS in signaling from neurons to intestine in ETC-deficient C. elegans. In addition to moving toward the characterization of mitokines, completion of the proposed work will (1) establish a highly-complementary collaboration between the Dillin and Arriaga groups, (2) introduce new bioanalytical resources to the Dillin Group, and (3) train Dr. Arriaga on the use of C. elegans to provide a new direction to complement Dr. Arriaga's age-related studies. Health relevance: There is compelling evidence that the longevity pathways in C. elegans are conserved in other more complex organisms including mammals. Thus, the findings of this research contribute to the understanding on how mitochondrial deficiencies in one tissue may activate stress responses in other tissue, which are extremely relevant to aging and age-related diseases. PUBLIC HEALTH RELEVANCE: Narrative Mitochondria deficiencies in the neurons of C. elegans activate a stress response in the intestine that is implicated in longevity. Stress responses are extremely relevant to aging and age-related diseases in humans.

描述（申请人提供）：土壤线虫秀丽隐杆线虫（秀丽隐杆线虫）是研究衰老过程的优秀模式生物。迪林小组使用的是缺乏电子传递链（ETC）的长寿命秀丽隐杆线虫突变体。当ETC缺陷只发生在神经元中时，线粒体特异性应激反应，即线粒体未折叠蛋白反应（UPRmt）在肠道中被激活，这反过来又需要维持突变体的延长寿命。上述秀丽隐杆线虫突变体的神经元和肠道之间的远距离协调表明存在一种信号分子（或多个分子），迪林小组将其称为“丝裂因子”。本F33应用探讨了以下假设：ETC缺陷秀丽隐杆线虫神经元中的线粒体ROS对于这些突变体肠道中分裂因子信号传导和UPRmt反应的激活至关重要。在迪林小组休假期间，Arriaga博士建议使用