MORPHOLOGICAL AND MOLECULAR CHANGES IN AGING COCHLEA

老化耳蜗的形态和分子变化

• 批准号: 6323328
• 负责人: BRAD SCHULTE
• 金额: $ 18.14万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6323328
• 关键词: aging; cochlea; gerbil /jird; human tissue; molecular genetics; morphology

Age-related hearing loss (presbyacusis) is among the most prevalent handicaps in humans over 65 years of age and will become an even greater health problem as population demographics shift towards the elderly. Studies of animal models of presbyacusis and of human temporal bones have provided a basic understanding of the histopathologic changes in the aging inner ear. However, knowledge about the primary cellular injury, the sequence of subsequent pathological events and the underlying molecular changes leading to loss of auditory function with age remains limited. This project proposes to address these issues through three specific areas of investigation. Aim 3.1 seeks to define the sequence of age-dependent histopathologic changes and to characterize age-related alterations in the expression of proteins in the gerbil cochlea. Aim 3.2 focuses on identifying and characterizing genes that show age-related alterations in their expression patterns in the gerbil inner ear. Aim 3.3 provides comparative data on human presbyacusis using similar approaches in studies of well-preserved, prospectively obtained human inner ears. The human studies will be driven by results obtained in Aims 3.1 and 3.2. The planned experiments will provide important new information concerning the cellular and molecular events leading to hearing loss in the elderly, and along with data obtained in Project 4, should form the rationale for designing pharmacological- gene-mediated therapies for the treatment and prevention of presbyacusis.

与年龄有关的听力损失（长期）是最普遍的 65岁以上的人类的障碍，将变得更大 人群人口的健康问题转向老年人。 对长老会和人类颞骨的动物模型的研究具有 提供了对组织病理学变化的基本理解 内耳衰老。 但是，有关主要细胞损伤的知识， 随后的病理事件和基础的序列 分子变化导致随着年龄的增长的听觉功能丧失 有限的。 该项目建议通过三个解决这些问题 特定调查领域。 AIM 3.1试图定义顺序 与年龄有关的组织病理学变化并表征与年龄相关的 沙鼠耳蜗中蛋白质表达的改变。 目标3.2 专注于识别和表征显示与年龄有关的基因 沙鼠内耳的表达模式改变。 目的 3.3使用类似的人提供有关人长期的比较数据 保存完好，前瞻性获得的研究中的方法 内耳。 人类研究将由目标获得的结果驱动 3.1和3.2。 计划的实验将提供重要的新 有关细胞和分子事件的信息导致 老年人的听力损失，以及项目4中获得的数据， 应形成设计药理基因介导的理由 用于治疗和预防长老会的疗法。