Age-related changes in C elegans nervous system & muscle

线虫神经系统与年龄相关的变化

• 批准号: 6815144
• 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/6815144
• 关键词: Caenorhabditis elegans; aging; biological signal transduction; cell age; gene expression; genetic screening; invertebrate locomotion; neuromuscular disorder; neuromuscular function; neuromuscular junction; neurons; phenotype

The goal of this project is to identify how aging affects neuronal and neuromuscular function. These studies are being performed using the nematode, C. elegans, which offers both genetic and cell biological approaches for studying this problem. In C. elegans, aging affects locomotory ability much more dramatically than sensory ability, which is relatively well-maintained during aging. The basis for this age-related locomotory deficit may be due to structural decline of the muscles or to impaired signaling at the neuromuscular junction. Both pharmacological and structural studies of aging neurons and muscles are being employed to investigate these possibilities. In addition, a genetic screen was conducted to identify genes that are required for normal age-related locomotory decline. This screen identified three mutants that appear to progress through aging faster than wild-type animals and one mutant that may be slowed in the progression of aging. Molecular identification of the genes mutated in these animals with accelerated or delayed-aging phenotypes will improve the understanding of the basis for age-related declines in movement and nervous system fuction.

该项目的目标是确定衰老如何影响神经元和神经肌肉功能。这些研究是使用线虫秀丽隐杆线虫进行的，它为研究这个问题提供了遗传和细胞生物学方法。对于秀丽隐杆线虫来说，衰老对运动能力的影响比对感觉能力的影响要大得多，而感觉能力在衰老过程中相对保持得很好。这种与年龄相关的运动缺陷的基础可能是由于肌肉结构衰退或神经肌肉接头信号受损所致。对衰老神经元和肌肉的药理学和结构研究正在被用来研究这些可能性。此外，还进行了基因筛查，以确定与年龄相关的正常运动能力下降所需的基因。该筛选鉴定出三种突变体，它们的衰老速度似乎比野生型动物更快，而一种突变体的衰老速度可能会减慢。对这些具有加速或延迟衰老表型的动物中突变​​的基因进行分子鉴定将提高对与年龄相关的运动和神经系统功能下降的基础的理解。