NEURODEGENERATION AND MITOCHONDRIAL DYSFUNCTION IN AGING

描述：(逐字摘自申请者摘要)神经退行性变 疾病包括通过事件促进病理过程 与正常衰老有关。衰老通常是一种必需的 伴随着神经系统疾病的进展，如果这是 如果发育迟缓，许多这类疾病的发生率将显著 减少了。防止赤字比防止赤字更容易实现 试图补偿受损的神经功能。这 应用假设大脑线粒体是一种易感基因 CSN内与年龄相关的促氧化剂事件的目标，即 外源性因素的应用可能会改变这些因素的速度 事件，这会影响其他生物和行为 老龄化的后果。 线粒体功能、结构完整性和成熟期的变化 线粒体DNA特性将在C57BL/6的整个生命周期内进行研究 老鼠。试图延缓线粒体变化的开始 参数包括基因缺失，膜稳定性和水平 关键的酶，将通过饮食补充抗氧化剂来制造， 专门针对保护产生的自由基 由于呼吸链的效率降低， 年事已高。结果将与以下结果相吻合： 神经细胞系暴露于低氧化剂后产生的线粒体 几代人的生活条件。活性氧和过氧化氢的作用 氮物种在这些事件中的贡献因素及其 抗氧化剂的潜在调节作用将被考虑在内。这个 复合抗氧化剂的保护潜力，目标是 氧化事件的几个来源，将被评估。 虽然神经系统疾病的发作通常并不代表 仅仅是正常衰老的加速，可能有生物学上的原因 两者都有共同之处。此类共同目标的确定和保护 将有助于开发能够减少发病率的药物 神经退行性疾病。

DESCRIPTION: (Verbatim from the Applicant's Abstract) neurodegenerative diseases involve promotion of a pathological process by events associated with normal aging. Senescence is generally an essential concomitant of the progression of neurological disease and if this were retarded, the incidence of many such disorders would be significantly reduced. Prevention of deficits is more readily accomplished than attempts to compensate for impaired neurological function. This application posits that the cerebral mitochondrion is a susceptible target of age-related pro-oxidant events within the CSN, that the administration of exogenous factors may modify the velocity of these events and that this can influence other biological and behavioral consequences of aging. Maturational changes in mitochondrial function, structural integrity and mtDNA characteristics will be studied throughout the lifespan of C57BL/6 mice. Attempts to retard the onset of changes in mitochondrial parameters including gene deletions, membrane stability and levels of key enzymes, will be made by dietary supplementation with antioxidants, specifically targeted toward protection against free radicals produced by the reduced efficiency of the respiratory chain encountered with advancing age. Results will be substantiated with those obtained from mitochondria derived from neural cell lines exposed to low oxidant conditions for several generations. The role of both active oxygen and nitrogen species as contributory factors in these events and their potential modulation by antioxidants will be taken into account. The protective potential of antioxidants in combination, targeted toward several sources of oxidative events, will be evaluated. While the onset of neurological disease generally does not represent merely an acceleration of normal aging, there may be biological loci common to both. The identification and protection of such common targets will help in the development of agents that can reduce the incidence of neurodegenerative disorders.