NEURODEGENERATION AND MITOCHONDRIAL DYSFUNCTION IN AGING

描述：（申请人摘要中的逐字记录）神经退行性 疾病涉及由事件促进的病理过程 与正常衰老有关。衰老通常是一个重要的 伴随着神经系统疾病的进展，如果这是 如果你是弱智，许多这类疾病的发病率将显着增加。 降低预防赤字比 试图弥补受损的神经功能。这 应用程序假定，大脑皮层是一个敏感的 CSN内与年龄相关的促氧化剂事件的目标， 外源性因素的管理可能会改变这些速度 这可能会影响其他生物和行为 老化的后果。 线粒体功能、结构完整性和 在C57 BL/6的整个生命周期中，将研究mtDNA特征 小鼠试图延缓线粒体变化的发生 参数包括基因缺失、膜稳定性和 关键酶，将通过饮食补充抗氧化剂， 专门针对保护免受自由基产生 由于呼吸链的效率降低， 年龄增长。结果将得到证实， 来自暴露于低氧化剂的神经细胞系的线粒体 几代人的条件。活性氧和 氮物种作为这些事件的贡献因子， 将考虑抗氧化剂的潜在调节。的 抗氧化剂组合的保护潜力，针对 将评价氧化事件的几个来源。 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， 两者都有。确定和保护这些共同目标 将有助于开发能够降低 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.