Biological Aging Mitrochondrial Variants and Coronary Artery Disease

该指导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人类年龄相关疾病遗传流行病学领域的独立调查员，特别是心血管疾病（CVD）。该候选人在统计遗传学领域非常成功。然而，她缺乏流行病学，衰老生物学和临床心脏病学的正式培训，这是人类慢性疾病杰出遗传流行病学家的三个关键组成部分。该补助金为广泛发展流行病学，心血管医学和衰老机制方面的技能提供了独特的机会。这些短期的职业目标将通过正式的课程工作，在协作环境中广泛的指导，以及研究计划的实施来实现，该研究计划将构成旨在调查线粒体基因多态性在生物衰老和CVD中的作用的更大研究的基础。该候选人目前在临床研究硕士（MSCR-KL 2）计划下，为她提供流行病学研究设计，混杂，临床数据库管理和慢性病流行病学方面的一年教学培训。在这个KOI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的正式培训。这一教学培训将得到拟议研究项目的补充，该项目首次提出血管相关遗传变异是血管老化、冠状动脉疾病（CAD）和主要不良心脏事件之间生物学联系的基础。该项目将利用在她的两位导师的指导下编制和维护的一个大型良好特征化的冠状动脉造影患者队列（1，000名患有显著CAD的患者和1，000名匹配对照）。具体目的是：1）检查端粒相关变异是否与端粒长度测量的生物学衰老有关; 2）确定端粒相关多态性是否与CAD和主要不良心脏事件相关。这个K 0 I奖将显着提高候选人的成长和成熟，成为一个独立的遗传流行病学家在人类衰老疾病，特别是心血管疾病。 相关性：冠状动脉疾病（CAD）是一种典型的衰老性疾病，是全球死亡和残疾的主要原因。生物老化和CAD之间的联系的识别不仅将提供新的见解衰老和CAD的病理生理学，但也可以确定新的生物标志物的老化和动脉粥样硬化，这可能最终改善预测，预防和治疗范围广泛的年龄相关疾病。

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.