Mitochondrial Dysfunction in Aging and Disease

描述（由申请人提供）：与年龄相关的人类疾病，包括癌症、阿尔茨海默病和帕金森病，与线粒体功能障碍和活性氧（ROS）有明显的相关性。我们建议采用遗传、生化和生物能量学相结合的方法来检验线粒体功能障碍，特别是线粒体活性氧（ROS）的产生与年龄相关疾病有关的假设。我们建议使用线粒体特征的三种主要操作——电子传递链复合物、谷胱甘肽库和超氧化物水平——来测量这三种与年龄相关的疾病的结果模型。

DESCRIPTION (provided by applicant): Age-related human diseases including cancer, Alzheimer's and Parkinson's disease show a clear correlation with mitochondrial dysfunction and reactive oxygen species (ROS). We propose to undertake a combined genetic, biochemical and bioenergetics approach to test the hypothesis that mitochondrial dysfunction and particularly mitochondrial reactive oxygen species (ROS) generation are causatively involved in age related disease. We propose to use three main manipulations of mitochondrial features-electron transport chain complexes, the glutathione pool and superoxide levels-and to measure outcomes models of these three age-related conditions. We believe that the proposed Program Project will make a significant contribution to our understanding of how mitochondrial function contributes to age-related disease with a view towards designing successful interventions.