STRESS PATHWAYS IN AGE-RELATED HEARING LOSS

年龄相关性听力损失的压力途径

• 批准号: 7475668
• 负责人: JOCHEN SCHACHT
• 金额: $ 126.54万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7475668
• 关键词: STRESS; PATHWAYS; AGE; RELATED; HEARING

DESCRIPTION (provided by applicant): Presbycusis, age-related hearing loss, is a major reason for social isolation and loss of quality of life in the elderly but we have neither a clear understanding of the mechanisms involved nor of strategies to prevent it. This program project brings together laboratories with long-standing interests in the biochemistry and molecular biology of stress pathways in the inner ear and a group of scientists with expertise in genetic studies in mice, for a series of interrelated studies of the fundamental cell biology and genetics of presbycusis. Project 1 (Antioxidant and homeostatic pathways) will test the hypothesis that antioxidant defenses and redox-sensitive signaling pathways decline with age rendering the inner ear more prone to cell injury and death. Project 2 (Stress pathways in the aging cochlea) extends this hypothesis to age-related changes in the classic stress response ("heat shock proteins"), by analyzing induced responses to stress during aging, and will generate new mouse models to examine this pathway in the cochlea. Project 3 (Genetic analysis of stress resistance and loss of hearing) focuses on the genetic controls and physiological regulators that modulate hearing loss in a population of genetically heterogeneous mice. Genotyping will provide a genomic map of loci modulating hearing acuity, its change over age, and its resistance to noise-induced damage. Specifically, the project will test the hypothesis that modulation of stress-resistance will modulate presbycusis. The projects will be supported by three cores. Core A (Administration) will coordinate reporting and evaluation activities and facilitate interactions among the projects. Core B (Physiology) will evaluate auditory function, and Core C (Otopathology/Histology) will assess morphological changes and provide histological assays. The three projects are taking distinct but complementary approaches to delineate the molecular and genetic basis of age-related hearing loss. The results will answer questions on the relationships among two well-characterized stress pathways in the aging cochlea, and identify new genetic loci associated with age-related hearing loss.

描述（由申请人提供）：与年龄相关的听力损失，老年人隔离和老年生活质量丧失的主要原因，但我们既不清楚地了解所涉及的机制，也不了解防止其策略。该计划项目汇集了对内耳应力途径的生物化学和分子生物学具有长期兴趣的实验室，以及一系列在小鼠遗传研究方面具有专业知识的科学家，对Persbycusis的基本细胞生物学和遗传学进行了一系列相互关联的研究。项目1（抗氧化剂和体内稳态途径）将检验以下假设：抗氧化剂防御和对氧化还原敏感的信号通路的下降，随着年龄的增长，内耳更容易容易出现细胞损伤和死亡。通过分析衰老过程中对压力的诱导响应，并将生成新的小鼠模型，以检查耳蜗中的这一途径，将该假设扩展到经典应力反应的年龄变化（“热休克蛋白”），将该假设扩展到与年龄相关的变化（“热激蛋白”），从而将该假设扩展到与年龄相关的变化，从而将该假设扩展到与年龄相关的变化。项目3（压力抵抗和听力丧失的遗传分析）着重于调节遗传异质小鼠群体听力损失的遗传控制和生理调节剂。基因分型将提供一个基因座调节敏锐度，其年龄变化以及其对噪声引起的损害的阻力的基因组图。具体而言，该项目将检验以下假设：压力抗性的调节将调节长老会。这些项目将得到三个核心的支持。核心A（管理）将协调报告和评估活动，并促进项目之间的互动。核心B（生理学）将评估听觉功能，核心C（眼科病理学/组织学）将评估形态学变化并提供组织学测定。这三个项目正在采用不同但互补的方法来描述与年龄相关的听力损失的分子和遗传基础。结果将回答有关老化耳蜗中两个良好特征应力途径之间关系的问题，并确定与年龄相关的听力损失相关的新遗传基因座。