Mitochondrial DNA Variation in Human Energy Expenditure and Metabolic Rate

人体能量消耗和代谢率中的线粒体 DNA 变化

基本信息

批准号：
7661736
负责人：
Gregory J. Tranah
金额：
$ 6.08万
依托单位：
CALIFORNIA PACIFIC MED CTR RES INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-15 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7661736
关键词：
ATP Synthesis Pathway Accounting Affect Age Aging Aging-Related Process Basal metabolic rate Base Pairing Bioenergetics Biological Blood Platelets Body Composition Brain Cardiovascular Diseases Cell Aging Cells Chromosomes, Human, Pair 16 Cohort Studies Collection Communities Coronary heart disease Coupling DNA DNA Resequencing Degenerative Disorder Detection Development Diabetes Mellitus Disease Elderly Endocrine system Energy Metabolism Event Genes Genetic Polymorphism Genome Germ Cells Haplogroup Health Heart Homeostasis Human Human body Impairment Incidence Indirect Calorimetry Intervention Juice Kidney Label Lead Life Link Longevity Malignant Neoplasms Measures Metabolic Mitochondria Mitochondrial DNA Mutate Mutation Nerve Degeneration Neurologic Nuclear Oxidative Phosphorylation Oxidative Stress Oxygen Pancreas Participant Phenotype Play Population Premature Mortality Primary Neoplasm Production Reactive Oxygen Species Risk Role Sampling Skeletal Muscle Somatic Mutation Testing Thermogenesis Time Urine Variant Water age related aged cell age clinically significant cost disability enzyme activity falls follow-up genetic variant meetings mitochondrial DNA mutation mortality neuromuscular public health relevance senescence

项目摘要

DESCRIPTION (provided by applicant): Higher free-living activity energy expenditure is strongly associated with lower risks of coronary heart disease, cancer incidence, falls, and mortality among older adults. It is unknown, however, how activity energy expenditure can protect older adults from physical disability and premature mortality. The importance of mitochondrial function to the rate of progression of age-related diseases such as cancer, diabetes, and neurodegeneration has become increasingly apparent in recent years. Yet little is currently known about the role of mtDNA mutations in human bioenergetics. Our primary aim is to assess the association of mtDNA polymorphisms and heteroplasmy with active energy expenditure and resting metabolic rate in the elderly. We will carry out our primary aim in a test of healthy samples from the Health, Aging and Body Composition (Health ABC) Study cohort. Active energy expenditure and resting metabolic rate were measured in 1998-1999 in 302 high-functioning, community-dwelling older adults (aged 70-82 years). We will use the recently developed Affymetrix Mitochondrial Resequencing Array v2.0 (MitoChip) to sequence the entire mtDNA genome of 200 study participants from the highest and lowest tertiles of free-living activity energy expenditure (>770 kcal/d and <521 kcal/d, respectively). The results of this study may directly link mtDNA mutations with energy expenditure and metabolic rate in the elderly and provide a mechanism by which specific mtDNA mutational events contribute to bioenergenic decline and subsequent mortality. The results of our study may have profound biological and clinical significance. Identifying genetic variants that influence energy expenditure and metabolic rate could eventually lead to interventions that prolong the productive and healthy years of human life. PUBLIC HEALTH RELEVANCE: Our primary aim is to assess the association of mtDNA polymorphisms and heteroplasmy with active energy expenditure and resting metabolic rate in the elderly. We will carry out our primary aim in a test of healthy samples from the Health, Aging and Body Composition (Health ABC) Study cohort. We will use the recently developed Affymetrix Mitochondrial Resequencing Array v2.0 (MitoChip) to sequence the entire mtDNA genome of 200 study participants from the highest and lowest tertiles of free- living activity energy expenditure. The results of this study may directly link mtDNA mutations with energy expenditure and metabolic rate in the elderly and provide a mechanism by which specific mtDNA mutational events contribute to bioenergenic decline and subsequent mortality.

描述（由申请人提供）：老年人中较高的自由生活活动能量消耗与较低的冠心病、癌症发病率、跌倒和死亡率风险密切相关。然而，尚不清楚活动能量消耗如何保护老年人免受身体残疾和过早死亡的影响。近年来，线粒体功能对癌症、糖尿病和神经退行性疾病等与年龄相关的疾病的进展速度的重要性日益明显。然而，目前人们对线粒体 DNA 突变在人类生物能学中的作用知之甚少。我们的主要目的是评估 mtDNA 多态性和异质性与老年人主动能量消耗和静息代谢率的关系。我们将通过对来自健康、衰老和身体成分 (Health ABC) 研究队列的健康样本进行测试来实现我们的主要目标。 1998-1999 年，对 302 名高功能社区居住老年人（70-82 岁）的主动能量消耗和静息代谢率进行了测量。我们将使用最近开发的 Affymetrix 线粒体重测序阵列 v2.0 (MitoChip) 对 200 名研究参与者的整个 mtDNA 基因组进行测序，这些参与者来自自由生活活动能量消耗的最高和最低三分位数（>770 kcal/d 和 <521 kcal/ d）。这项研究的结果可能直接将 mtDNA 突变与老年人的能量消耗和代谢率联系起来，并提供了特定 mtDNA 突变事件导致生物能下降和随后死亡的机制。我们的研究结果可能具有深远的生物学和临床意义。识别影响能量消耗和代谢率的基因变异最终可能会导致延长人类生命的生产力和健康年限的干预措施。公共健康相关性：我们的主要目的是评估 mtDNA 多态性和异质性与老年人主动能量消耗和静息代谢率的关系。我们将通过对来自健康、衰老和身体成分 (Health ABC) 研究队列的健康样本进行测试来实现我们的主要目标。我们将使用最近开发的 Affymetrix 线粒体重测序阵列 v2.0 (MitoChip) 对 200 名研究参与者的整个 mtDNA 基因组进行测序，这些参与者来自自由生活活动能量消耗的最高和最低三分位。这项研究的结果可能直接将 mtDNA 突变与老年人的能量消耗和代谢率联系起来，并提供一种特定 mtDNA 突变事件导致生物能下降和随后死亡的机制。