MTDNA DAMAGE AND REPAIR IN CALORIC RESTRICTED MICE

热量限制小鼠的 MTDNA 损伤和修复

基本信息

批准号：
6707426
负责人：
SYLVETTE AYALA-TORRES
金额：
$ 2.32万
依托单位：
UNIVERSIDAD CENTRAL DEL CARIBE
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-03-01 至 2003-08-31
项目状态：
已结题

项目摘要

Functional Senescence: Genetic, cellular and biochemical basis of functional senescence Oxygen radicals cause damage to DNA, primarily to mitochondrial DNA and this damage can lead to mitochondrial dysfunction. It has been suggested that oxidative mitochondrial DNA and this damage can lead to mitochondrial dysfunction. It has been suggested that oxidative mitochondrial DNA damage is a major contributor to age-associated loss of brain function in the mouse. So far, caloric restriction-life span extension remains unknown. Preliminary studies using quantitative polymerase chain reaction show an age-associated increase in basal levels brain mitochondrial DNA damage. In addition, aged mice exhibit a lower repair capacity induction after induction of oxidative damage by the mitochondrial inhibitor 3-nitropropionic acid. The purpose of this pilot study is to determine if caloric restriction reduces oxidative DNA damage in mouse brain mitochondria and prevents further oxidative stress. The hypothesis predicts that caloric restriction will enhance the mitochondrial DNA repair capacity and therefore reduce the age-associated accumulation of mitochondrial DNA damage. To test this hypothesis the following aims will be addressed: 1) Determine the extent of mitochondrial DNA damage and repair in the brain during aging and caloric restriction in mice, 2) Examine the effect of caloric restriction on the induction of oxidative mitochondrial DNA damage by the mitochondrial inhibitor 3-nitropropionic acid, and 3) Examine mitochondrial function in caloric function in caloric mice. This pilot project will assist in laying the foundation for a research project directed towards the understanding of the effect of caloric restriction in the extension of mammalian life span.

功能性衰老：功能性衰老氧自由基的遗传，细胞和生化基础对DNA造成损害，主要是对线粒体DNA的损害，而这种损伤可能导致线粒体功能障碍。已经提出氧化线粒体DNA及其损伤会导致线粒体功能障碍。已经提出，氧化线粒体DNA损伤是小鼠中与年龄相关的脑功能丧失的主要原因。到目前为止，热量限制寿命扩展仍然未知。使用定量聚合酶链反应的初步研究表明，基础水平与脑线粒体DNA损伤相关。此外，老年小鼠在线粒体抑制剂3-硝基丙酸诱导氧化损伤后表现出较低的修复能力诱导。这项试验研究的目的是确定热量限制是否会减少小鼠脑线粒体中的氧化DNA损伤并防止进一步的氧化应激。该假设预测热量限制将增强线粒体DNA修复能力，从而减少与年龄相关的线粒体DNA损伤的积累。要检验该假设，将解决以下目的：1）确定小鼠衰老和热量限制期间的线粒体DNA损伤和修复的程度，2）检查热量限制对氧化性线粒体DNA诱导的影响，通过线粒体抑制剂3-硝化剂的氧化型DNA损伤，检查量表和3硝基化的量表。该试点项目将有助于为一个研究项目奠定基础，该项目致力于理解哺乳动物寿命范围内热量限制的影响。