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

描述(由申请者提供)：本NRSA中建议的培训包括实践研究和教学部分。研究部分的主要目的是确定代谢综合征(METS)的存在和严重性在多大程度上导致衰老相关的功能下降，并检查这种关系是否由过度炎症介导。由于维持身体机能是老年人保持独立能力的关键因素，该项目的研究部分与NIA的使命高度相关。该项目将通过对Health ABC研究中收集的数据进行二次分析来完成，该研究是一个由3075名功能正常的白人和黑人老年人(70-79岁)组成的前瞻性队列，具有MET的特征，包括几个身体功能和炎症指数。具体地说，该项目将(1)确定蛋氨酸的存在和严重程度(成分的数量)是否与基线时的身体功能低下以及随着时间的推移老年人的身体功能下降有关；(2)确定蛋氨酸的存在和严重程度是否与基线的炎症有关，以及是否与老年人的炎症随时间的变化有关；以及(3)确定炎症是否以及在多大程度上降低了蛋氨酸对身体功能的影响。统计方法包括Logistic回归和混合效应建模，以及中介分析。该项目将为候选人提供一个实际机会，利用她将作为拟议课程的一部分学习的统计和流行病学技能(如下所述)。这项研究还将为应聘者提供数据管理和纵向数据分析方面的直接、实际经验。在教学部分，比弗斯博士将完成维克森林大学公共卫生科学部和翻译科学研究所临床和人口翻译科学硕士项目提供的一系列课程，内容包括统计学、流行病学和临床试验，如临床和翻译科学基础、流行病学、临床试验方法和应用线性模型。完成这些课程将对统计学和流行病学概念以及临床试验方法有更全面的了解，使比弗斯博士能够在未来的职业生涯中构思、计划和执行临床研究。研究结果将更好地描述蛋氨酸、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努力，而临床和人口翻译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，并培养指导和翻译临床和人口研究的能力。 公共卫生相关性：维持身体机能是老年人保持独立能力的关键因素。更好地描述代谢综合征等常见可预防疾病与身体功能障碍之间的关系，对于旨在预防残疾的努力至关重要。鉴于65岁及以上人口不断增长，再加上与年龄相关的身体功能丧失带来的经济和情感负担，迅速确定可改变的功能衰退风险因素是相当大的公共卫生问题。

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.