Does Kidney Function Determine Aging Success

描述(由申请人提供)：作为心血管健康研究(CHS)肾脏工作组的一部分，我们已经表明，由血清肌酐确定的肾功能水平与炎症标志物以及临床和亚临床心血管疾病(CVD)有关。我们最近还检测了胱抑素-C，这是一种更敏感、更新颖的肾功能测量方法。这使得我们在了解肾功能对年龄相关健康的影响程度方面取得了重大突破。虽然血清肌酐水平只检测到肾功能损害最严重的一小部分老年个体，但胱抑素-C似乎与几个衰老风险因素以及亚临床和临床心血管疾病存在线性关联。这些发现表明，肾功能可能在决定衰老成功的过程中发挥核心作用。 这项建议是对肾功能的纵向评估，通过半胱氨酸氨基转移酶-C的测量，以及它与CHS患者18年随访成功老龄化的关系。我们还将评估胱抑素-C与衰老危险因素(炎症、其他血管和身体成分危险因素)、亚临床疾病(心血管、脑血管和肌肉骨骼)、临床疾病(心血管、脑血管和肌肉骨骼)以及身体和认知功能减退率的变化的关系。我们假设肾功能将是衰老成功的主要和独立的决定因素，范围从保存良好(低胱抑素-C)到一般(中等胱抑素-C)到肾功能差(高胱抑素-C)。 我们的具体目标是：评估由胱抑素-C测定的肾功能连续测定与成功衰老维持的关系；评价胱抑素-C连续测定与不成功衰老危险因素纵向变化的关系；评价胱抑素-C连续测定与亚临床疾病纵向变化的关系；评价连续测定胱抑素-C与临床疾病随访的关系。 统计分析显示，每个目标都有足够的力量。肾脏工作组包括一组CHS的高级和新的研究人员，以及心血管、老年和肾脏相关流行病学等学科。该小组在推进肾脏疾病研究方面发挥了重要作用。因此，该小组有能力在拟议的时间范围内成功完成各项目标。 与公共健康相关：肾功能异常常见于老年人。我们有一种新的检测方法，半胱氨酸氨基转移酶-C，可以准确地评估肾功能水平。这项应用的目的是评估胱抑素-C是否与衰老并发症有关。如果是这样的话，保存肾功能可能是成功衰老的关键。

DESCRIPTION (provided by applicant): As part of The Renal Working Group of the Cardiovascular Health Study (CHS), we have shown that levels of kidney function, as ascertained by serum creatinine, are associated with inflammatory markers as well as clinical and subclinical cardiovascular disease (CVD). We have recently also measured cystatin-C, a more sensitive and novel measure of kidney function. This has allowed a major breakthrough in our understanding of the extent to which kidney function impacts age-related health. Whereas serum creatinine evels only detect a small subset of elderly individuals with the most impaired kidney function, cystatin-C appears to have a linear association with several aging risk factors, as well as subclinical and clinical CVD. These findings suggest that kidney function may play a central role in determining aging success. This proposal is a longitudinal assessment of kidney function, as measured by cystatin-C, and its relationship to successful aging over 18 years of follow-up in CHS. We will also evaluate the relationship of cystatin-C to changes in aging risk factors (inflammatory, other vascular and body compositional risk factors), subclinical disease (cardiovascular, cerebrovascular and musculoskeletal), clinical disease (cardiovascular, cerebrovascular and musculoskeletal) and rates of decline in physical and cognitive function. We hypothesize that kidney function will be a major and independent determinant of aging success across the spectrum from well-preserved (low cystatin-C) to average (medium cystatin-C) to poor kidney function (high cystatin-C). Our specific aims are as follows: To evaluate the relationship of serial measurements of kidney function, as determined by cystatin-C, to maintenance of successful aging; to evaluate the relationship between serial measurements of cystatin-C with longitudinal changes in risk factors for unsuccessful aging; to evaluate the relationship between serial measurements of cystatin-C with longitudinal changes in subclinical disease; to evaluate the relationship between serial measurements of cystatin-C with clinical disease in follow-up. Statistical analyses reveal adequate power for each of the aims. The Renal Working Group includes a group of both senior as well as new investigators to CHS, and disciplines including cardiovascular, geriatric and kidney-related epidemiology. The group has played an important role in advancing research in kidney disease. The team is therefore capable of successfully completing the aims within the time frame proposed. Relevance to public health: Abnormalities in kidney function are frequently found in older adults. We have a novel test, cystatin-C, that accurately assesses level of kidney function. The goal of this application is to evaluate whether cystatin-C is associated with complications of aging. If so, preservation of kidney function may be key to successful aging.