Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)

描述（由申请人提供）：心血管健康研究（CHS）全明星研究的修订竞争性更新的目标是确定衰老如何在系统中展开并预测无残疾生存期。基于1992/93年和1998/99年之间所作的观察，并在随后的15年内，系统内和跨系统的无残疾生存相关的变化，我们将寻求确定所观察到的变化是否是上游疾病事件的预测因子，是并发疾病的变化，或适应性反应，维持稳态。所提出的方法将允许设计针对关键发病率的预防干预策略，并在与年龄相关的功能下降可改变的时间窗口内通过相关生物标志物进行跟踪。具体目标是：1.继续随访CHS队列中剩余的1260名男性和女性，以描述其长期生存和无残疾生存的特征。这将提供一个准确的评估率和预测的非常长的活跃和残疾寿命的整体和性别，种族和出生队列。2.确定与长期生存和无残疾生存相关的亚临床疾病指标和衰老生物标志物的水平和变化。我们将评估衰老生物标志物的变化是否可由现有疾病解释，与亚临床疾病标志物同时变化，和/或预测未来的死亡率和残疾，独立于亚临床疾病。3.使用亚临床疾病和衰老生物标志物的重复测量，检查多个系统变化之间的对应关系。我们假设亚临床疾病和衰老生物标志物的测量结果显著聚集在具有最长无残疾生存期的个体中。我们将探索新的代谢因素，以进一步解决能量稳态是生存的关键这一假设。

DESCRIPTION (provided by applicant): The goal of this revised competing renewal for the Cardiovascular Health Study (CHS) All Stars Study is to determine how aging unfolds across systems and predicts disability-free survival. Based on observations made between 1992/93 and 1998/99 and relating changes within and across systems to disability-free survival over the subsequent 15 years, we will seek to determine whether observed changes are upstream predictors of disease events, are concurrent with disease changes, or are adaptive responses that maintain homeostasis. The proposed approach will allow the design of prevention intervention strategies aimed at pivotal morbidities and tracked by associated biomarkers in a window of time where age related functional decline is modifiable. The specific aims are: 1. To continue to follow the remaining 1260 men and women in CHS cohort to characterize their long term survival and disability-free survival. This will provide an accurate assessment of rates and predictors of very long active and disabled life span overall and by sex, race and birth cohort. 2. To determine the levels and changes in subclinical disease measures and aging biomarkers that are associated with long term survival and disability free survival. We will evaluate whether changes in aging biomarkers are explained by existing disease, change concurrently with subclinical disease markers, and/or predict future mortality and disability, independently of subclinical disease. 3. To examine the correspondence between changes across multiple systems, using repeated measures of subclinical disease and biomarkers of aging. We hypothesize that measures of subclinical disease and biomarkers of aging significantly cluster in the individuals with the longest term disability free survival. We will explore novel metabolic factors to further address the hypothesis that energy homeostasis is key to survival.