Mitochondrial Antioxidants, Aging and Healthspan

描述（由申请人提供）：这个长期项目项目的更新申请是基于一个高度集中、综合和互动的研究假设，即线粒体抗氧化剂能够抵抗与年龄相关的疾病，并改善哺乳动物多器官系统的健康和功能。这建立在过去的进展基础上，包括观察到过表达线粒体靶向过氧化氢酶的小鼠延长了寿命，改善了心脏和肌肉健康，并提高了对上皮癌的抵抗力。因此，我们越来越关注健康和健康跨度，包括研究器官功能衰退的急性模型，这些模型可以作为衰老过程中类似疾病的替代检测方法。在本项目中，我们提出了四个项目，将该方法应用于线粒体活性氧（ROS）和ROS诱导的损伤起重要作用的衰老疾病：1)线粒体ROS和心脏老化；2)线粒体ROS与神经退行性疾病；3)线粒体ROS与衰老对上皮细胞癌的保护作用；4)线粒体靶向抗氧化剂、衰老和AZT在骨骼肌功能障碍中的作用。项目由四个核心支撑：1)行政；2)小鼠病理生物学；3)蛋白质组学;4)线粒体保护化学。在这些项目和核心中，我们试图了解线粒体ROS在衰老和健康中的作用机制，并追求鉴定线粒体保护药物的转化目标，以向人类提供这些健康益处。

DESCRIPTION (provided by applicant): This application for renewal of our longstanding Program Project is based on a highly focused, integrated and interactive effort to examine the hypothesis that mitochondrial antioxidants are capable of resisting age-related disease and improving health and function in multiple organ systems in mammals. This builds on past progress, including observations that mice overexpressing mitochondrially targeted catalase have extended lifespan, improved cardiac, and muscle health and resistance to epithelial cancers. We therefore have developed an increasing focus on health and healthspan, including study of acute models of decline in organ function that can serve as surrogate assays for similar disorders in aging. In this Program Project we propose four Projects to apply this approach to disorders of aging in which mitochondrial reactive oxygen species (ROS) and ROS-induced damage play an important role: 1) Mitochondrial ROS and cardiac aging; 2) Mitochondrial ROS and neurodegenerative disease; 3) Mitochondrial ROS and protection from epithelial cancers in aging; 4) Mitochondrial-targeted antioxidants, aging and AZT in skeletal muscle dysfunction. The Projects are supported by four Cores: 1) Administrative; 2) Mouse pathobiology; 3) Proteomics; 4) Mitochondrial protective chemistry. In each of these Projects and Cores we seek to understand the mechanisms underlying the role of mitochondrial ROS in aging and healthspan, as well as pursuing the translational goal of identifying mitochondrial protective drugs to deliver these healthspan benefits to humans.