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

• 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
• 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

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）：在老年人中，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，活动性能量消耗如何保护老年人免于身体残疾和过早死亡尚不清楚。近年来，线粒体功能对年龄相关疾病（如癌症、糖尿病和神经退行性疾病）进展速度的重要性越来越明显。然而，目前对mtDNA突变在人类生物能量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。我们将在健康、衰老和身体成分（Health ABC）研究队列中对健康样本进行测试，以实现我们的主要目标。研究人员于1998-1999年对302名生活在社区的老年人（70-82岁）进行了主动能量消耗和静息代谢率的测量。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，从自由生活活动能量消耗的最高和最低三分位数（分别为70 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量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。确定影响能量消耗和代谢率的基因变异，最终可能导致延长人类生产和健康寿命的干预措施。公共卫生相关性：我们的主要目的是评估老年人mtDNA多态性和异质性与活跃能量消耗和静息代谢率的关系。我们将在健康、衰老和身体成分（Health ABC）研究队列中对健康样本进行测试，以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，从自由活动能量消耗的最高和最低三分位数开始。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量下降和随后死亡的机制。