REGULATION OF ENERGY METABOLISM IN AGING AND DISEASE--CENTRAL NERVOUS SYSTEM

该项目研究了老年人和老年人的线粒体功能， 在病理状态下， 线粒体可能危及神经元的存活。 我们已经调查 主要缺失（4.8 Kb）的发生频率 线粒体（mt）DNA在四个确定的脑区域（大脑皮层， 小脑，海马和纹状体），作为衰老的功能， 大鼠 线粒体DNA编码的复合体I，III和IV的亚单位， 线粒体呼吸链以及复合物V（ATP- 合成酶）、核糖体和t-RNA。 主要缺失的程度 我们已经研究过的是， 不能为受影响的DNA分子;然而，互补 在同一个DNA分子中， 发生. 我们发现随着年龄的增长，大约6岁，10岁和20岁- 4.8 Kb缺失的发生率增加一倍，占总缺失的比例 基因组，当大脑皮层，海马和纹状体，分别， 在6月龄和22-23月龄大鼠中进行比较。 但 缺失的基因组仍然只占总数的很小一部分 (less 1%以上，老年人。 无论它们在世界上是否重要， 组织的功能可能取决于（a）分布是否 是偶数，或者相反，如果在神经元之间存在镶嵌现象，以及（B） 也阻止转录的其他形式突变的互补 线粒体DNA 这是一个与C.F.博士合作的项目。LBC的Filburn，NIA。

This project examines mitochondrial functioning in old age and in pathological states in which decreased energy transduction by mitochondria may compromise survival of neurones. We have investigated the frequency of occurrence of a major deletion (4.8 Kb) in mitochondrial (mt) DNA in four defined brain regions (cerebral cortex, cerebellum, hippocampus and striatum), as a function of aging in the rat. mt-DNA codes for subunits of complexes I, III and IV of the mitochondrial respiratory chain as well as complex V (the ATP- synthase), ribosomal and t-RNA's. The magnitude of the major deletion which we have studied is such as to make transcription completely incompetent for the affected DNA molecule; however, complementation with other DNA molecules within the same mitochondrion is likely to occur. We found increases with aging of approximately 6, 10 and 20- fold in the incidence of the 4.8 Kb deletion, as a fraction of total genomes, when cerebral cortex, hippocampus and striatum, respectively, were compared in 6 month and 22-23 month old rats. However, the deleted genomes still represent a very small fraction of the total (less than 1%) in old-age. Whether they are important in the functioning of the tissue likely depends upon (a) whether distribution is even, or if instead there is mosaicism among neurons, and (b) the complement of other forms of mutation which also prevent transcription of mt-DNA. This is a joint project with Dr. C.F. Filburn of LBC, NIA.