Control of life span and nervous system aging in C.elega

线虫寿命和神经系统衰老的控制

• 批准号: 6667918
• 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/6667918
• 关键词: Caenorhabditis elegans; aging; biological signal transduction; developmental neurobiology; genetic regulation; insulin; longevity; mutant; nervous system; neurogenetics; neurotransmitters; phosphatidylinositol 3 kinase

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. To determine how neurons control lifespan, we are isolating mutant animals that live shorter or longer than the 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. Recently, we have succeeded isolating candidate mutants from these studies. A second goal of this project is to identify genes required for successful aging in the nervous system. Successful aging in humans can be thought of as increasing resistance to aging-associated neurodegenerative diseases, such as Alzheimers and Parkinsons diseases. We have begun by characterizing how the C. elegans nervous system changes during aging. We have found that there are three stages to nematode adulthood: a reproductive phase, a mid-life phase and a late-life phase that preceeds death. The most dramatic aging-associated changes occur in the mid-life phase, and these may involve changes in neurotransmitter activity. We are currently studying why the neurotransmitter activity appears to change in the mid-life stage. These studies of aging in the relatively simple organism, C. elegans, will provide a stepping stone for understanding the more complex processes that control human aging and lifespan.

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。为了确定神经元如何控制寿命，我们正在分离比长寿胰岛素通路突变体寿命更短或更长的突变动物。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。最近，我们已经成功地从这些研究中分离出候选突变体。 该项目的第二个目标是确定神经系统中成功衰老所需的基因。人类的成功衰老可以被认为是对衰老相关的神经退行性疾病（如阿尔茨海默病和帕金森病）的抵抗力增加。我们已经开始描述如何C。线虫的神经系统在衰老过程中发生变化。我们发现线虫的成年期有三个阶段：生殖阶段、中年阶段和死亡前的晚期阶段。最显著的衰老相关变化发生在中年阶段，这些变化可能涉及神经递质活性的变化。我们目前正在研究为什么神经递质活动似乎在中年阶段发生变化。这些关于相对简单的生物体C.这将为理解控制人类衰老和寿命的更复杂的过程提供一块垫脚石。