Genetic Analysis of Drosophila Functional Aging

果蝇功能衰老的遗传分析

• 批准号: 8448791
• 负责人: ROLF BODMER
• 金额: $ 8.44万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8448791
• 关键词: Address; Administrative Personnel; Affect; Age; Aging; Aging-Related Process; Biological Assay; Biological Models; Biometry; California; Cardiac; Cardiovascular system; Cessation of life; Communities; Complex; Consult; Consultations; Cutaneous; Data Analyses; Development; Disease; Drosophila genus; Drosophila melanogaster; Elderly; Endocrine; Epilepsy; Expenditure; Frequencies; Funding; Future; Gene Expression Regulation; Genetic; Genetic Models; Genetic Screening; Gerontology; Goals; Growth; Human; Huntington Disease; Immune; Individual; Insulin; Lead; Leadership; Longevity; Lung; Maintenance; Mathematics; Methods; Modeling; Monitor; Morbidity - disease rate; Pathology; Peripheral; Phenotype; Physiological; Principal Investigator; Process; Progress Reports; Protocols documentation; Reagent; Regulation; Reporting; Research; Resource Allocation; Rodent; Role; Services; Signal Transduction; Sleep; Structure; System; Time; Transduction Gene; Transgenic Organisms; Universities; Variant; Work; Writing; age related; base; body system; cancer type; cell motility; cell type; fly; functional decline; genetic analysis; genetic manipulation; human disease; meetings; mortality; mutant; neuropathology; operation; programs; reproductive; senescence; statistical service; tool; web page

DESCRIPTION (provided by applicant): Aging leads to degenerative change in multiple systems and cell types. These losses induce the functional decline of specific physiological systems that contribute to progressive morbidity and ultimately to death. Two fundamental questions for basic gerontology arise from these central observations. What are the processes of intrinsic physiological decline in structure and function that lead to the eventual expression of specific geriatric disorders? To what extent are different phenotypes of functional aging coordinately regulated by common factors of an underlying aging process? This program project will address these questions with integrated research on functional aging of a genetic model system, Drosophila melanogaster. To achieve this goal, our program has four overall aims. 1) Establish multiple models of functional aging in Drosophila melanogaster with high physiological relevance to human senescent phenotypes, specifically in the senescence of cardiac, immune and sleep. 2) Assess how insulin/IGF and TOR regulation of lifespan affects independent and conglomerate axes of functional aging. 3) Discover pathogenic mechanisms underlying age dependent decline in cardiac, immune and sleep by methods of genetic manipulation including forward genetic screens and transgenic analysis of candidate factors. 4) Assess whether apparently divergent, asynchronous aspects of functional senescence are driven by a common process of aging. REVIEW OF INDIVIDUAL COMPONENTS OF THE PROGRAM PROJECT CORE A: ADMINISTRATIVE CORE, Dr. Rolf Bodmer, Core Leader (CL) DESCRIPTION (provided by applicant): Core A has the role to provide the leadership, interaction and coordination between the different projects of this PPG in order to facilitate them in meeting their scientific goals. Core A will oversee the organization of bi-annual meetings of the project leaders, organize annual meetings of the project leaders with the Scientific Advisory Board (SAB) and to review progress on the overall goals of the PPG as a whole. The PI of this PPG assisted by administrative personnel will assure seamless operation of the scientific agenda and administrative matters. Core A will also provide the administrative support, which includes the monitoring of funds and research allocations. The PI will review expenditures and resource allocations for the projects and cores, at least twice a year. The administrative core will also be responsible for collating the reports from the scientific advisory boards, as well as writing and transmitting the annual progress report to NIA. The PI of Core A will consult with a statistician from the nearby Department of Mathematics at the University of California at San Diego to provide statistical services. These services will be sought for consultation in biostatistical analysis of data from the various assays of the projects (for example, PCR, cardiac pacing, gut motility, sleep bout frequency, and many more). In addition, Core B leader Dr. Tatar and Dr. Gibson, a qualitative geneticist, will provide expert advice in biostatistics. Core A will oversee the launch and maintenance of a Web page for this PPG, which will allow distribution of findings among the global community, while enabling sharing protocols, reagents as well as information among the projects in real time.

描述（由申请人提供）：衰老导致多种系统和细胞类型的退行性变化。这些损失会导致特定生理系统的功能下降，从而导致进行性发病并最终导致死亡。基础老年学的两个基本问题产生于这些中心观察。导致特定老年疾病最终表达的内在生理结构和功能衰退的过程是什么？在多大程度上，功能性衰老的不同表型是由潜在衰老过程的共同因素协调调节的？本项目将通过对遗传模型系统——黑腹果蝇的功能衰老进行综合研究来解决这些问题。为了实现这一目标，我们的计划有四个总体目标。1)建立与人类衰老表型具有高度生理相关性的黑腹果蝇功能衰老的多种模型，特别是在心脏、免疫和睡眠衰老方面。2)评估胰岛素/IGF和TOR对寿命的调控如何影响功能性衰老的独立轴和综合轴。3)通过基因操作方法，包括正向基因筛选和候选因子转基因分析，发现心脏、免疫和睡眠年龄依赖性衰退的致病机制。4)评估明显不同的、不同步的功能性衰老是否由一个共同的衰老过程驱动。