MECHANISMS OF CELLULAR DEGENERATION IN AGING

衰老过程中细胞退化的机制

• 批准号: 3821491
• 负责人: GARY S LYNCH
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 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/3821491
• 关键词: aging; brain metabolism; calcium channel blockers; calcium metabolism; cerebellum; electrophysiology; hippocampus; hypothalamus; lipofuscin; mitochondria; monoclonal antibody; neurochemistry; peptidases; pons; pyruvate dehydrogenase

The goal of this project is to characterize the biochemical events underlying nerve cell degeneration during aging. Specific attention focuses upon two mechanisms, which may be related. Primary emphasis is directed towards calcium-activated proteases (calpain) which can degrade cytoskeletal structures. Calpain activity and levels will be assayed in different brain regions of numerous animal species using enzymatic assay procedures and antibody binding techniques; the data will then be compared to cell degeneration in the particular areas and to the expected lifespan of the species. Calpain's role in the aging process will then be inferred from these results. In related studies, the activity of lysosomal proteases will also be assayed. Further experiments are designed to examine the distribution and the physiological consequence of lipofuscin or lipofuscin-like dence-body accumulations in the brain. Using morphometric methods, the extent of dense-body accumulation will be related to cell loss, calpain levels, and lysosomal protease activities. In addition, electrophysiological parameters, such as membrane potential and resistance, evoked e.p.s.p. amplitudes, and so forth will be examined in hippocampal neurons containing pharmacologically induced dense-body accumulations. Causal relationships between these various phenomena may be deduced for the collected results.

这个项目的目标是描述生物化学事件 衰老过程中神经细胞的退化 具体关注重点 这两种机制可能是相关的。 主要重点是 对钙激活蛋白酶（钙蛋白酶），可以降解细胞骨架 结构. 钙蛋白酶活性和水平将在不同的大脑中进行测定 许多动物物种的区域使用酶测定程序， 抗体结合技术;然后将数据与细胞 退化的特定领域和预期寿命的 物种 钙蛋白酶在衰老过程中的作用可以从 这些结果。 在相关研究中，溶酶体蛋白酶的活性将 也可以化验。 进一步的实验旨在研究 脂褐素的分布和生理后果， 脑内脂褐素样瘤体堆积。 使用形态测量 方法，致密体积累的程度将与细胞损失有关， 钙蛋白酶水平和溶酶体蛋白酶活性。 此外，本发明还提供了一种方法， 电生理参数，例如膜电位和电阻， 诱发的e. p. s. p.振幅等将在海马 神经元内含有大量诱导的致密体堆积。 这些不同现象之间的因果关系可以推断为 收集结果。