Telomere Length Dynamics in Relation to Changes in Adiposity and Metabolic Risk

端粒长度动态与肥胖和代谢风险变化的关系

• 批准号: 9262669
• 负责人: JOANNE E. CURRAN
• 金额: $ 65.88万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9262669
• 关键词: Adipose tissue; Adult; Age; Aging; Biological; Biological Aging; Biological Markers; Biology; Blood Chemical Analysis; Body Composition; Body fat; Body mass index; Cardiovascular Diseases; Cell Aging; Chronic; Chronic Disease; Data; Disease; Elderly; Epidemic; Family; Female; Functional disorder; Genes; Genetic; Glucose; Goals; Growth; Health; Human; Inflammation; Interleukin-6; Knowledge; Lead; Length; Leukocytes; Life Style; Link; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Metabolic; Metabolic Marker; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Participant; Pathway interactions; Pattern; Peripheral Blood Mononuclear Cell; Phenotype; Play; Prevention; Public Health; Quantitative Trait Loci; Randomized; Regulation; Research; Research Design; Resources; Risk; Risk Assessment; Risk Factors; Role; Running; Sampling; Single Nucleotide Polymorphism; Societies; Stromal Cell-Derived Factor 1; Telomerase; Telomere Shortening; Time; Visceral; Visit; abdominal fat; age related; base; cancer type; cohort; cost effective; disorder risk; follow-up; genetic pedigree; genetic variant; genome-wide; inflammatory marker; innovation; male; novel; novel therapeutics; phenotypic data; potential biomarker; risk variant; senescence; subcutaneous; telomere; trait; whole genome

PROJECT SUMMARY Telomere length and telomerase activity have been posited as biomarkers for cellular aging, longevity, and age-related conditions such as cardiovascular disease and type 2 diabetes. Their role in the pathophysiology of chronic diseases, however, is still not well-defined, as they have been shown to also be influenced by adiposity. Moreover, information on the role of genetics in telomere biology is scarce. The objectives of the proposed study are to explore the phenotypic and genotypic relationship between body composition measures (e.g., obesity) and telomere length and telomerase activity, and to investigate the role of telomere length and telomerase activity on metabolic risk factors and disease in adults. Using a longitudinal study design, we propose to measure serial leukocyte telomere length (LTL) from already existing stored (n=4204) and newly collected (n=1000) buffy coat samples in 1794 Fels Longitudinal Study participants ranging in age from 18-93 years. Fels Longitudinal Study participants have been repeatedly measured over their entire lifetime for body composition and metabolic markers. Over time, more advanced measures of body composition such as visceral and subcutaneous abdominal adiposity using MRI, and novel blood chemistries such as inflammatory markers have been also been collected. Whole genome single nucleotide polymorphism (SNP) data are available on a large subset of these participants to search for genes influencing telomere biology. This uniquely valuable cohort presents a readily available, cost-effective, and powerful resource for understanding the relationship between telomere biology and cardiometabolic health. The specific aims of the proposed study are: 1) to examine longitudinal associations between adiposity traits, telomere length, and metabolic risk in 1794 adults, 2) to examine cross-sectional relationships between newly collected telomerase activity, telomere length, adiposity traits, and metabolic risk factors in a subset (N=1000) of participants, and 3) to identify genetic variants influencing telomere length and telomerase activity and to use Mendelian Randomization to examine causal associations among obesity, telomere biology and metabolic risk in a subset (N=1247) of study participants. The results of this proposed study will provide important information about how telomere biology is linked to obesity, aging, and cardiometabolic disease risk. Further, this information will aid in the assessment of risk, prevention and treatment of accelerated aging and chronic disease.

项目概要 端粒长度和端粒酶活性已被认为是细胞衰老、长寿和健康的生物标志物。 与年龄相关的疾病，例如心血管疾病和 2 型糖尿病。它们在病理生理学中的作用 然而，慢性病的发病率仍然没有明确的定义，因为它们已被证明也受到以下因素的影响： 肥胖。此外，关于遗传学在端粒生物学中的作用的信息很少。该计划的目标 拟议的研究旨在探索身体成分测量之间的表型和基因型关系 （例如肥胖）和端粒长度和端粒酶活性，并研究端粒长度和端粒酶活性的作用 端粒酶活性对成人代谢危险因素和疾病的影响。 使用纵向研究设计，我们建议测量连续白细胞端粒长度（LTL） 1794 年费尔斯纵向已有存储的 (n=4204) 和新采集的 (n=1000) 血沉棕黄层样本 研究参与者的年龄范围为 18 至 93 岁。费尔斯纵向研究的参与者已多次被 在他们的整个一生中测量身体成分和代谢标志物。随着时间的推移，更加先进 使用 MRI 测量身体成分，例如内脏和皮下腹部脂肪，以及新颖的 还收集了血液化学成分，例如炎症标记物。全基因组单一 这些参与者的大部分都可以使用核苷酸多态性 (SNP) 数据来搜索基因 影响端粒生物学。这个具有独特价值的群体提供了一个易于获得、具有成本效益且 了解端粒生物学与心脏代谢健康之间关系的强大资源。 拟议研究的具体目的是：1）检查肥胖之间的纵向关联 1794 名成年人的性状、端粒长度和代谢风险，2) 检查之间的横截面关系 新收集的端粒酶活性、端粒长度、肥胖特征和代谢危险因素的子集 (N=1000) 参与者，以及 3) 识别影响端粒长度和端粒酶活性的遗传变异 并使用孟德尔随机化来检查肥胖、端粒生物学和 研究参与者子集 (N=1247) 的代谢风险。 这项拟议研究的结果将提供有关端粒生物学如何与 肥胖、衰老和心脏代谢疾病的风险。此外，这些信息将有助于风险评估， 预防和治疗加速衰老和慢性疾病。