The Effects of Resveratrol on Presbyacusis

白藜芦醇对老年性耳聋的作用

• 批准号: 6680568
• 负责人: Michael D. Seidman
• 金额: $ 17.88万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6680568
• 关键词: NAD(P)H dehydrogenase; aging; antioxidants; auditory stimulus; biological products; biotherapeutic agent; brain stem; diet therapy; ear hair cell; flavonoids; flow cytometry; free radical oxygen; high performance liquid chromatography; laboratory rat; lipoxygenase; membrane potentials; mitochondrial DNA; organ of Corti; oxidation reduction reaction; polymerase chain reaction; presbycusis; prostaglandin endoperoxide synthase; respiratory enzyme; sound perception; spectrometry; western blottings

DESCRIPTION (provided by applicant): The primary purpose of this project is to study the long-term effect of resveratrol, the antioxidant compound found in red wine, on age-related hearing loss. Presbyacusis is a progressive deterioration of hearing loss associated with aging and is the most common cause of adult auditory deficiency in the United States. 23% of the population between ages 65 and 75 years and 40% of the population older than 75 years are affected. Compelling evidence suggests that aging-related diseases progress due to the accumulation of reactive oxygen species (ROS). ROS are primarily produced in vivo during mitochondrial respiration, the process that provides energy to cells. ROS cause damage to mitochondrial DNA (mtDNA), resulting in the production of specific mtDNA deletions and mutations; these produce bioenergetically deficient cells. Ultimately, this persistent attack of ROS on mitochondrial and cellular structures results in cell death, tissue damage and hearing loss. Isolated grape constituents such as resveratrol, catechins and flavanols are noted for their antioxidant and anti-inflammatory properties and their potential for preventing cancer and heart disease. Resveratrol is 20 times more potent than Vitamin C and has been found to be more effective at preventing oxidative DNA damage than any other antioxidant. By decreasing the activity of Complex 3 of mitochondrial oxidative phosphorylation chain, it opposes the production of ROS and scavenges them. This protects against age-related nerve changes. Preliminary studies conducted in our laboratory have shown that resveratrol protects against noise-induced hearing loss as well. This project will study the effects of resveratrol on mitochondrial and auditory functions. We hypothesize that aged animals that have been treated with resveratrol will have improved auditory sensitivity and mitochondrial function and reduced inner ear hair cell loss compared to control animals. The differences in auditory sensitivity will be studied by auditory brainstem response measurements. The differences in mitochondrial function will be studied by measuring the mitochondrial membrane potentials, mitochondrial respiratory enzyme level (complex 1) and mtDNA deletions. We will also study the expression of 5-lipoxygenase, cyclooxygenase 1 and 2 as indirect measures of ROS generation. These studies will provide the foundation for developing clinical studies to investigate the use of antioxidants and mitochondrial-function enhancing nutritional supplements to attenuate auditory deterioration in patients with presbyacusis. Furthermore, these data will provide novel strategies to impart greater wellness in the elderly population and perhaps have a positive effect on health care expenses.

描述（由申请人提供）：该项目的主要目的是研究白藜芦醇（红酒中发现的抗氧化剂化合物）对年龄相关的听力损失的长期影响。长老会是与衰老相关的听力损失的逐步恶化，是美国成人听觉缺乏的最常见原因。 65至75岁之间的人口中有23％的人口受到75岁以上人口的影响。令人信服的证据表明，由于活性氧（ROS）的积累，与衰老相关的疾病的进展。 ROS主要在线粒体呼吸过程中在体内产生，该过程为细胞提供能量。 ROS会损害线粒体DNA（mtDNA），从而产生特定的mtDNA缺失和突变。这些会产生生物能缺乏的细胞。最终，ROS对线粒体和细胞结构的这种持续攻击导致细胞死亡，组织损伤和听力损失。白藜芦醇，儿茶素和黄烷醇等分离的葡萄成分因其抗氧化剂和抗炎特性而闻名，及其预防癌症和心脏病的潜力。白藜芦醇的效力是维生素C的20倍，并且被发现比任何其他抗氧化剂更有效地预防氧化DNA损伤。通过减少线粒体氧化磷酸化链的复合物3的活性，它会反对ROS的产生并清除它们。这可以防止与年龄相关的神经变化。在我们的实验室中进行的初步研究表明，白藜芦醇也可以防止噪声引起的听力损失。该项目将研究白藜芦醇对线粒体和听觉功能的影响。我们假设与对照动物相比，用白藜芦醇治疗的老年动物将提高听觉敏感性和线粒体功能，并减少内耳毛细胞的损失。听觉敏感性的差异将通过听觉脑干响应测量来研究。线粒体功能的差异将通过测量线粒体膜电位，线粒体呼吸酶水平（复合物1）和mtDNA缺失来研究。我们还将研究5-脂氧酶，环氧酶1和2作为ROS产生的间接度量的表达。这些研究将为开发临床研究提供基础，以调查使用抗氧化剂和线粒体功能增强营养补充剂的使用，以减轻长老会患者的听觉恶化。此外，这些数据将提供新颖的策略，以在老年人口赋予更大的健康状况，并可能对医疗保健费用产生积极影响。