Control of Gene Expression and Life Span

项目摘要/摘要 我们的长期目标是了解决定基因和分子的因素 衰老和寿命的过程。这项提议的重点是识别分子 介导卡路里/饮食限制(CR/DR)寿命延长的遗传效应 开发分子遗传学和药理学干预的先决条件 延长健康寿命。多种物种的CR/DR检测显示 大量的基因和生理系统。翻译这篇文章的一个核心问题 治疗干预的信息是所看到的许多变化中的哪些涉及到 在延长健康寿命方面？在果蝇中，分子遗传学研究导致了一种模型 CR/DR延长寿命效应的一部分是由 组蛋白去乙酰基酶Rpd3和Sir2以及转录因子P53的活性。 该模型提供了一个框架，用于识别遗传、生化和 CR/DR的药理效应分子介导了长寿。在本提案中，我们将：(I) 进一步研究dsir2的增加延长了 Fly，(Ii)确认通过我们的基因组鉴定的基因的延长寿命的效果 分析CR/Sir2/P53通路并初步确定其与CR/DR的关系 延长寿命，(三)利用基于基因组的工具来确定基因和基因集 对延长果蝇CR/DR寿命的重要作用和(Iv)测试这些新技术的效果 使用分子遗传学工具识别与寿命有关的基因。

Project Summary / Abstract Our long-term goal is to understand the genetic and molecular elements that determine the process of aging and life span. The focus of this proposal is to identify molecular genetic effectors that mediate calorie/dietary restriction (CR/DR) life span extension as a prerequisite to developing molecular genetic and pharmacological interventions that can extend healthy life span. Examination of CR/DR in a variety of species shows changes in a large number of genes and physiological systems. A central question in translating this information to therapeutic interventions is which of the many changes seen are involved in extending healthy life span? In flies molecular genetic studies have lead to a model in which a portion of the life span extending effect of CR/DR is mediated by alterations in the activity of the histone deacetylases Rpd3 and Sir2, and the transcription factor p53. This model provides a framework for use in identifying genetic, biochemical, and pharmacological effectors of CR/DR mediated longevity. In this proposal we will (i) further examine the mechanisms by which an increase in dSir2 extends life span in the fly, (ii) confirm the life span extending effect of a gene identified through our genomic analysis of the CR/Sir2/p53 pathway and begin to determine it's relationship to CR/DR life span extension, (iii) utilize genome based tools to determine genes and gene sets important for CR/DR life span extension in flies and (iv) test the effect of these newly identified genes on life span using molecular genetic tools.