Genetic analysis of lifespan control by insulin-like sig

类胰岛素信号控制寿命的遗传分析

• 批准号: 6968974
• 负责人: Catherine A Wolkow
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6968974
• 关键词: Caenorhabditis elegans; aging; biological signal transduction; genetic mapping; genetic regulation; insulin; longevity; molecular cloning; mutant; neural degeneration; neurogenetics; neurotransmitters; phosphatidylinositol 3 kinase; transcription factor

Lifespan in the nematode, C. elegans, is determined by interacting genetic pathways as well as by environmental conditions. For example, mutations in the daf-2/insulin-like signaling pathway nearly triple adult lifespan. One goal of this project is to learn why these mutants live longer. It has been shown that insulin signaling must be active in the C. elegans nervous system for normal lifespan, suggesting that neurons somehow control lifespan. One goal of this project is to identify the neurons that dictate lifespan via insulin-like signaling. A second goal of this project is to define new genes that collaborate with the insulin-like pathway. To this end, several new mutations were isolated that lengthen or shorten lifespan of long-lived insulin pathway mutants. These mutants will enable us (a) to identify the genes that are required for a long adult lifespan and (b) to identify previously unknown pathways that influence adult lifespan. Many basic biological processes are shared between nematodes and humans. Therefore, some of the genes that control lifespan in the worm may also have human versions that perform similar functions. The genes mutated in these altered-lifespan mutants are currently being mapped and cloned for molecular characterization.

线虫的寿命，C.线虫，是由相互作用的遗传途径以及环境条件。例如，daf-2/胰岛素样信号通路的突变几乎使成年人的寿命增加了三倍。这个项目的一个目标是了解为什么这些突变体活得更长。已经表明，胰岛素信号传导必须在C。这表明神经元以某种方式控制寿命。该项目的一个目标是识别通过胰岛素样信号决定寿命的神经元。该项目的第二个目标是确定与胰岛素样途径合作的新基因。为此，分离出了几种新的突变，这些突变延长或缩短了长寿胰岛素途径突变体的寿命。这些突变体将使我们能够（a）鉴定出延长成年人寿命所需的基因，（B）鉴定出以前未知的影响成年人寿命的途径。许多基本生物学过程在线虫和人类之间是共享的。因此，蠕虫中控制寿命的一些基因也可能具有执行类似功能的人类版本。目前正在对这些寿命改变的突变体中发生突变的基因进行定位和克隆，以进行分子表征。