Role of metabolic syndrome and inflamamation on physical function in the elderly

描述（由申请人提供）：NRSA中提出的培训包括实践研究和教学部分。该研究部分的主要目的是确定代谢综合征（MetS）的存在和严重程度在多大程度上导致与衰老相关的功能衰退，并检查这种关系是否由过度炎症介导。由于身体功能的维持是老年人保持独立能力的关键因素，因此本项目的研究部分与NIA的使命高度相关。该项目将通过对健康ABC研究中收集的数据进行二次分析来完成，该研究是一项前瞻性队列研究，包括3075名功能良好的白人和黑人老年人（70-79岁），具有良好的MetS特征，身体功能和炎症的几个指标。具体而言，该项目将(1)确定MetS的存在和严重程度（成分数量）是否与基线时较低的身体功能以及老年人随着时间的推移身体功能下降有关；(2)确定MetS的存在和严重程度是否与基线时的炎症以及随时间的炎症变化有关；(3)确定炎症是否以及在多大程度上降低MetS对身体功能的影响。统计方法包括逻辑回归和混合效应模型，以及中介分析。该项目将为候选人提供一个实际的机会，利用她将在拟议课程（如下所述）中学习的统计和流行病学技能。该研究还将为候选人提供数据管理和纵向数据分析方面的直接实践经验。在教学方面，Beavers博士将完成维克森林大学公共卫生科学和转化科学研究所的临床和人口转化科学硕士课程提供的一系列课程，包括统计学、流行病学和临床试验，如临床和转化科学基础、流行病学、临床试验方法和应用线性模型。完成这些课程将提供对统计和流行病学概念以及临床试验方法的更全面的理解，使Beavers博士能够在她未来的职业生涯中概念化，计划和执行临床研究。研究结果将更好地描述MetS、炎症和身体功能之间的关系，这可能有助于为患有功能性残疾的老年男性和女性制定预防和治疗措施。而临床和人口转化科学课程提供了一个独特的机会，可以最大限度地提高候选人在维克森林大学的博士后培训，并培养临床和人口研究的指导和翻译能力。

DESCRIPTION (provided by applicant): The training proposed in this NRSA contains both a practical research and didactic component. The broad aim of the research component is to determine the extent to which the presence and severity of metabolic syndrome (MetS) contributes to aging-related functional decline, and to examine whether this relationship is mediated by excess inflammation. Because maintenance of physical function is a critical factor in the ability of older adults to remain independent, the research component of this project is highly relevant to the mission of the NIA. The project will be accomplished via secondary analyses of data collected in the Health ABC Study, a prospective cohort of 3,075 well-functioning white and black elders (70-79 years), well characterized for MetS, with several indices of physical function and inflammation. Specifically, this project will (1) determine whether the presence and severity (number of components) of MetS is associated with lower physical function at baseline and with a decline in physical function over time in older adults; (2) determine whether the presence and severity of MetS is associated with inflammation at baseline and with changes in inflammation over time in older adults; and (3) determine whether, and to what degree, inflammation reduces the effect of MetS on physical function. Statistical methods to be used include logistic regression and mixed effects modeling, as well as mediation analysis. This project will provide a practical opportunity for the candidate to utilize the statistical and epidemiological skills she will learn as part of the proposed coursework (described below). The research will also provide the candidate with direct, practical experience in data management and longitudinal data analysis. For the didactic component, Dr. Beavers will complete a series of courses offered through the Master's program in Clinical and Population Translational Sciences at the Division of Public Health Sciences and Translational Science Institute at Wake Forest University in statistics, epidemiology, and clinical trials, such as Foundations of Clinical and Translational Science, Epidemiology, Clinical Trial Methods, and Applied Linear Models. Completion of these courses will provide a more comprehensive understanding of statistical and epidemiological concepts and clinical trial methodology, allowing Dr. Beavers to be able to conceptualize, plan, and execute clinical research in her future career. The research findings will provide better characterization of the relationship between MetS, inflammation, and physical function, which may assist in the development of preventive and therapeutic efforts for older men and women with functional disability, while the coursework in Clinical and Population Translational Sciences offers a unique opportunity to maximize the candidate's post-doctoral training at Wake Forest University and develop competencies in conduction and translation of clinical and population research. PUBLIC HEALTH RELEVANCE: Maintenance of physical function is a critical factor in the ability of older adults to remain independent. Better characterization of the relationship between common preventable conditions, such as metabolic syndrome, and physical dysfunction is critical to efforts aimed at preventing disability. Given the growing demographic of persons aged 65 years and older, coupled with the economic and emotional burden related to age-associated loss of physical function, prompt identification of modifiable functional decline risk factors is of considerable public health concern.