Does Kidney Function Determine Aging Success

肾功能决定衰老成功吗

• 批准号: 7125098
• 负责人: MARK J SARNAK
• 金额: $ 31.48万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125098
• 关键词: aging; biomarker; body physical activity; cardiovascular disorder; cerebrovascular disorders; clinical research; cognition; creatine; creatinine; disease /disorder proneness /risk; growth factor receptors; human data; human tissue; inflammation; kidney function; longitudinal human study; musculoskeletal disorder; protease inhibitor; statistics /biometry

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.

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，我们已经证明，通过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）相关。我们最近还测量了胱抑素c，这是一种更敏感和新颖的肾功能测量方法。这使得我们对肾脏功能影响年龄相关健康的程度的理解有了重大突破。血清肌酐水平只能检测一小部分肾功能受损最严重的老年人，而胱他汀- c似乎与几种衰老危险因素以及亚临床和临床心血管疾病呈线性相关。这些发现表明，肾脏功能可能在决定衰老成功方面发挥核心作用。