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Role of Mitochondrial DNA Mutations in Aging in Neuronal Cells

线粒体 DNA 突变在神经细胞衰老中的作用

基本信息

批准号：
7795071
负责人：
Yidong Bai
金额：
$ 28.88万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-01 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7795071
关键词：
Age Aging Aging-Related Process Apoptosis Applications Grants Biochemical Biogenesis Brain Brain region Cell Culture System Cell Line Cell model Cell physiology Cells DNA Electron Transport Energy Supply Evaluation Exhibits Functional disorder Gene Mutation Generations Genes Genetic Genetic Transcription Goals Individual Lipids Measures Methods Mitochondria Mitochondrial DNA Molecular Molecular Genetics Monitor Mus Mutation Nerve Endings Neuroblastoma Neurons Nuclear Oxidative Phosphorylation Oxidative Stress Phenotype Physiological Proteins Reactive Oxygen Species Regulation Relative (related person)Reporting Respiration Role Sequence Analysis Signal Transduction Synaptosomes System Technology Testing Time Tissues Translations age group age related established cell line human tissue improved insight middle age mitochondrial DNA mutation mitochondrial dysfunction mitochondrial genome mutant oxidative damage programs respiratory theories

项目摘要

Our long-term goal is to study the role of mitochondria in aging. The overall goal of this grant application is to test the mitochondria! theror/ of aging and, in particular, to investigate the role of mitochondrial DNA(mtDNA) mutations in mouse brain during aging. As one of the most favored hypotheses, the mitochondrial theory of aging, predicts that somatic mitochondria DNA (mtDNA) mutations accumulate with time, and the compromised mitochondrial function resulting from these mutations is then responsible for various aging phenotypes. However, there has been no comprehensive study of the overall accumulation of mtDNA mutations during aging, and the physiological consequences of aging-related mtDNA mutations are largely unclear. We recently established a method to transfer mtDNA from mouse nerve endings, i.e., synaptosomes to a cell system, and we have improved methods to isolate and characterize mtDNA mutations. Combined with established mitochondrial molecular genetic and biochemical technologies, we can, for the first time, investigate the accumulation of mtDNA mutations in neuronal cells during aging by evaluating individual mtDNA from the synaptosomes.The particular hypothesis to be tested in this proposal is that mutations in the mitochondrial genome accumulate during aging in mouse neuronal cells; these mtDNA mutations in turn compromise mitochondrial function and may result in oxidative damage to various cellular components including mtDNA in neuronal cells. We will perform genetic and functional analyses of aging-related mtDNA mutations by transferring synaptosomal mtDNA to a cell line system. This will reveal low frequncy mtDNA mutations that could not be identified by other methods. By generating neuronal cell models that carry aging-related mtDNA mutations, we will also charaterize the physiological consequences of the mutations, in particular those related to oxidative damage. The successful completion of this project will not only help to test the mitochondrial theory of aging, but could also provide insights into the underlying mechanisms of the aging process.

我们的长期目标是研究线粒体在衰老中的作用。这项奖助金申请的总体目标是