Age-related inflammatory changes: The role of genes and body composition changes

描述（由申请人提供）：本提案旨在量化炎症基因和身体成分变化对炎症标志物年龄相关变化的影响。炎症与许多影响老年人的疾病和状况有关，包括动脉粥样硬化性心血管疾病（ASCVD）。炎症活动随着年龄的增长而增加，然而，关于这种变化的自然历史及其起源和后果的知识是非常有限的。我们假设炎症标志物的年龄相关变化部分可以通过肥胖和炎症基因多态性的年龄相关变化来解释，并且可能是后续ASCVD的重要危险因素。健康老龄化和身体组成（Health ABC）研究是一项前瞻性研究，对3075名70多岁的黑人和白人，男性和女性进行纵向数据分析，自1997- 1998年以来每年进行一次随访，将使我们能够有效地实现以下具体目标：1)确定7年随访期间炎症标志物随年龄变化的模式；2)测试观察到的炎症标志物的变化在多大程度上可归因于脂肪量或内脏脂肪的增加和炎症基因多态性；3)确定炎症标志物年龄相关变化对后续ASCVD事件的预测能力。拟议的研究将包括所有健康ABC参与者。对于目的1和2，我们将每两年测量一次血清c反应蛋白和白细胞介素-6水平，并对大约29个参与炎症和先天免疫反应的重要基因进行变异测序。我们将使用线性混合效应模型进行纵向数据分析。对于目标3，将使用Cox比例风险模型进行前瞻性分析。了解免疫衰老及其心血管恶化的年龄相关改变正变得越来越重要，并可能为治疗干预提供基础，这些干预不仅会影响ASCVD的风险，还会影响老年人其他常见疾病（如糖尿病、痴呆、虚弱和残疾）的发病率和死亡率。健康ABC研究是唯一对社区居住的老年人进行长期随访和每年详细测量身体成分的大型队列研究，以及广泛的功能、临床和实验室数据，为研究这一高度科学优先领域提供了独特的机会。

DESCRIPTION (provided by applicant): This proposal aims to quantify the effects of inflammatory genes and body composition changes on age-related changes in inflammatory markers. Inflammation has been implicated in a number of diseases and conditions that affect older adults including atherosclerotic cardiovascular disease (ASCVD). Inflammatory activity increases with aging, however, the knowledge about the natural history of this change and its origins and consequences is extremely limited. We postulate that age-related changes in inflammatory markers are partially explained by age-related changes in adiposity and inflammatory gene polymorphisms, and may be an important risk factor for subsequent ASCVD. Longitudinal data analyses using the Health Aging and Body Composition (Health ABC) Study, a prospective study of 3,075 black and white, men and women in their seventies who have been followed annually since 1997-98, will allow us to efficiently achieve the following specific aims: 1) to determine the pattern of changes in inflammatory markers with age during 7 years of follow-up; 2) to test the extent to which observed changes in inflammatory markers can be attributed to increase in fat mass or visceral fat and inflammatory gene polymorphisms; 3) to determine the predictive ability of age-related changes in inflammatory markers on subsequent ASCVD events. The proposed study will include all the Health ABC participants. For aim1 and 2, we will conduct measures of serum C-reactive protein and interleukin-6 levels every two years and sequence variants of approximately 29 important genes involved in inflammation and innate immune response. We will perform longitudinal data analyses using linear mixed-effect models. For aim 3, a prospective analysis will be conducted with Cox proportional hazard model. Understanding age-related alterations in immunosenescence and its cardiovascular deterioration is becoming increasingly important and may provide the basis for therapeutic interventions that will impact not only risk of ASCVD, but will impact morbidity and mortality from other common diseases of the elderly such as diabetes, dementia, frailty and disability. The Health ABC study, the only large cohort of community-dwelling older adults with long term follow-up and annually detailed measures of body composition, along with a wide range of functional, clinical, and laboratory data, provides a unique opportunity for studying this area of high scientific priority.