Biological Aging Mitrochondrial Variants and Coronary Artery Disease

生物衰老线粒体变异和冠状动脉疾病

• 批准号: 7708450
• 负责人: Jinying Zhao
• 金额: $ 13.14万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7708450
• 关键词: Affect; Age; Aging; Angiography; Area; Atherosclerosis; Award; Biogenesis; Biological; Biological Aging; Biological Markers; Biology; Biology of Aging; Blood Vessels; Cardiac; Cardiology; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Chronic Disease; Clinical; Clinical Research; Clinical Trials; Complement; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Coronary artery; Data Analyses; Data Base Management; Development; Disease; Environment; Epidemiologic Studies; Epidemiologist; Epidemiology; Event; Functional disorder; Genes; Genetic; Genetic Polymorphism; Goals; Grant; Growth; Human; K-Series Research Career Programs; Length; Link; Master of Science; Measures; Medicine; Mentors; Mentorship; Mitochondria; Outcome; Pathway interactions; Patients; Phenotype; Predisposition; Prevention; Research; Research Design; Research Personnel; Research Project Grants; Role; Scientist; Severities; Time; Training; Variant; Work; Writing; age related; atherogenesis; base; career; cohort; disability; genetic epidemiology; genetic variant; improved; insight; novel; programs; skills; telomere

DESCRIPTION (provided by applicant): This mentored research scientist career development award (KOI) proposal is a four-year plan to enable the candidate to develop into an independent investigator in the field of genetic epidemiology for human age-related disorders, in particular cardiovascular disease (CVD). The candidate has been very successful in the area of statistical genetics. However, she lacks formal training in epidemiology, aging biology and clinical cardiology, three crucial components for an outstanding genetic epidemiologist in human chronic disorders. This grant provides a unique opportunity for extensive development of skills in epidemiology, cardiovascular medicine and aging mechanism. These short term career goals will be accomplished through formal course work, extensive mentorship in a collaborative environment, and implementation of a research plan that will form the basis of a larger study aimed at investigating the role of mitochondrial gene polymorphisms in biological aging and CVD. The candidate is currently covered under a Master of Science in Clinical Research (MSCR-KL2) Program which provides her one year didactic training in epidemiological study design, confounding, clinical database management, and chronic disease epidemiology. During the first year of this KOI, she will continue formal training in clinical trials, epidemiological data analysis, grant writing, biology of CVD and aging as well as clinical cardiology. This didactic training will be complemented by the proposed research project, which proposes for the first time that mitochondrial-related genetic variants underlie the biological links among vascular aging, coronary artery disease (CAD) and major adverse cardiac events. This project will take advantage of a large well- characterized patient cohort for coronary angiography (1,000 patients with significant CAD and 1,000 matched controls) that has been compiled and maintained under the direction of her two mentors. The specific aims are 1) To examine whether mitochondrial-related variants are implicated in biological aging measured by telomere length; and 2) To determine whether mitochondrial-related polymorphisms are associated with CAD and major adverse cardiac events. This K0I award will significantly enhance the candidate's growth and maturation into an independent genetic epidemiologist in human aging disorders, in particular cardiovascular disease. RELEVANCE: Coronary artery disease (CAD), a typical aging disorder, is the leading cause of death and disability worldwide. Identification of the link between biological aging and CAD will not only provide novel insights into the pathophysiology of aging and CAD, but may also identify new biomarkers for aging and atherogenesis, which may, ultimately, improve prediction, prevention and treatment of a wide range of age-related disorders.

描述（由申请人提供）：这项受过指导的研究科学家职业发展奖（KOI）提案是一项为期四年的计划，旨在使候选人能够发展成为针对人类年龄相关疾病的遗传流行病学领域的独立研究者，特别是心血管疾病（尤其是心血管疾病（CVD））。候选人在统计遗传学领域非常成功。但是，她缺乏流行病学，衰老生物学和临床心脏病学的正式培训，这是人类慢性疾病中出色遗传流行病学家的三个关键组成部分。该赠款为流行病学，心血管医学和衰老机制的大量发展提供了独特的机会。这些短期职业目标将通过正式的课程工作，在协作环境中进行广泛的指导以及实施研究计划来实现，该计划将构成一项旨在研究生物衰老和CVD中线粒体基因多态性作用的更大研究的基础。该候选人目前均由临床研究硕士（MSCR-KL2）计划涵盖，该计划为她在流行病学研究设计，混杂，临床数据库管理和慢性疾病流行病学方面提供了一年的教学培训。在此锦鲤的第一年，她将继续在临床试验，流行病学数据分析，赠款写作，CVD和衰老生物学以及临床心脏病学方面进行正式培训。拟议的研究项目将补充这种教学训练，该项目首次提出了与线粒体相关的遗传变异，是血管衰老，冠状动脉疾病（CAD）和重大不良心脏事件之间生物学联系的基础。该项目将利用冠状动脉血管造影术（1,000例具有显着CAD和1,000个匹配对照的患者）的大量特征性的患者队列，该患者已在她的两位导师的指导下进行了编译和维护。具体目的是1）检查线粒体相关的变体是否与端粒长度测量的生物老化有关； 2）确定线粒体相关的多态性是否与CAD和重大不良心脏事件有关。该K0I奖将显着增强候选人的成长和成熟，成为人类衰老疾病，尤其是心血管疾病的独立遗传流行病学家。 相关性：典型的衰老疾病冠状动脉疾病（CAD）是全球死亡和残疾的主要原因。鉴定生物衰老与CAD之间的联系不仅可以为衰老和CAD的病理生理学提供新的见解，而且还可以鉴定出用于衰老和动脉粥样硬化的新生物标志物，这最终可能会改善与年龄相关疾病的广泛预测，预防和治疗。