Epidemiology of lens aging in older women

老年女性晶状体老化的流行病学

• 批准号: 7998549
• 负责人: JASON Leigh SANDERS
• 金额: $ 4.64万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7998549
• 关键词: Adult; Age; Aging; Aging-Related Process; Animal Model; Atherosclerosis; Benchmarking; Biological Process; Caloric Restriction; Cardiovascular Diseases; Cataract; Cell Aging; Chronic; Chronic Disease; Cohort Studies; Communities; Coronary Arteriosclerosis; Crystallins; Densitometry; Development; Diabetes Mellitus; Disease; Elderly; Epidemiologic Studies; Epidemiology; Functional disorder; Future; Goals; Human; Individual; Inflammation; Insulin; Interleukin-6; Intervention Studies; Investigation; Length; Lens Diseases; Lens Opacities; Leukocytes; Measures; Metabolic Marker; Molecular; Morbidity - disease rate; Participant; Performance; Photography; Population; Postmenopause; Research; Research Personnel; Risk Factors; Skin; System; Testing; Tissues; Vascular Diseases; Whole Organism; Woman; age effect; base; cognitive function; cohort; fasting glucose; genetic manipulation; human population study; in vivo; lens; lens transparency; mortality; novel; older women; public health relevance; telomere

DESCRIPTION (provided by applicant): It is critical to determine how we age if we hope to optimize the wellbeing of individuals, particularly older adults who represent a growing proportion of the population. Traditionally, studying aging was equated with unalterable decline and the development of disease. Although it is uncertain if the primary effects of aging can be fully distinguished from the secondary effects of disease, recent research has identified that aging and disease are not synonymous, and subsequently that aging can be optimized. This has been most clearly demonstrated in animal models with genetic manipulation and caloric restriction. In these systems mortality rate has been the primary marker of aging, but for human studies in vivo markers of aging are needed. Few primary markers of aging have been validated in human population studies. Aging of the lens, as assessed using lens transparency, has been proposed as a reflection of aging because it is detectable in early to mid adulthood and can be distinguished from known diseases of the lens, including specific types of cataract. The goal of this epidemiologic study is to determine the association of lens transparency with measures of disease and measures of aging in a cohort of older women. These will include atherosclerosis, a marker of vascular disease, and fasting glucose and insulin, markers of metabolic dysfunction. Additionally, telomere length and interleukin-6, markers of cellular senescence and chronic inflammation, respectively, will represent underlying biological processes that contribute to aging across tissues. If lens transparency is strongly related to these factors, it will provide evidence that transparency reflects cardiovascular disease or diabetes, and/or biological processes underlying aging. Finally, we will examine if lens opacity is associated with physical or cognitive function, markers of performance that indicate organismal aging independent of disease. For this investigation, we will conduct a cross-sectional cohort study in participants of the Healthy Women Study (HWS), a community-based longitudinal cohort study that began in 1983-84 and was just refunded for a 4th examination of the determinants of risk factor changes among women during peri- and postmenopause. To capitalize on the wealth of information obtained in the HWS during the current study cycle, we will add a measure of lens transparency using Scheimpflug photography, which uses linear densitometry to provide a quantitative measure of transparency. Validating lens transparency as a primary marker of aging will allow future researchers to employ it as a benchmark in unraveling the aging process, potentially as a novel intermediate marker for human intervention studies. PUBLIC HEALTH RELEVANCE: With this research we aim to determine the association of lens transparency to measures of cardiovascular disease and diabetes, the leading chronic disease causes of morbidity and mortality in the world, and to leukocyte telomere length, interleukin-6, and markers of physical and cognitive function, which illustrate aging on molecular and whole organism levels. Our results will help validate lens transparency as a primary marker of aging, disease, both, or neither; this is important because few primary markers of aging exist and none are measured in vivo, like lens transparency, which thus has the potential to more accurately reflect aging. Determining whether lens transparency is a primary marker of aging will allow future researchers to employ it as a benchmark in unraveling the aging process and could serve as a standard against which to test indicators of and modulators of aging in the hopes of optimizing aging.

描述（由申请人提供）：如果我们希望优化个人的福祉，特别是占人口比例不断增长的老年人，那么确定我们如何变老至关重要。传统上，研究衰老等同于不可改变的衰退和疾病的发展。尽管不确定是否可以完全区分衰老的主要影响和疾病的次要影响，但最近的研究发现衰老和疾病不是同义词，因此可以优化衰老。这在基因操作和热量限制的动物模型中得到了最清楚的证明。在这些系统中，死亡率一直是衰老的主要标志，但对于人类研究，需要体内衰老标志。在人口研究中，很少有衰老的主要标志得到验证。使用晶状体透明度评估的晶状体老化被认为是老化的反映，因为它可以在成年早期到中期检测到，并且可以与已知的晶状体疾病（包括特定类型的白内障）区分开来。这项流行病学研究的目的是确定老年女性群体中晶状体透明度与疾病测量和衰老测量之间的关系。这些包括动脉粥样硬化（血管疾病的标志）以及空腹血糖和胰岛素（代谢功能障碍的标志）。此外，端粒长度和白介素 6（分别是细胞衰老和慢性炎症的标志物）将代表导致跨组织衰老的潜在生物过程。如果晶状体透明度与这些因素密切相关，它将提供透明度反映心血管疾病或糖尿病和/或衰老背后的生物过程的证据。最后，我们将检查晶状体混浊是否与身体或认知功能相关，这是表明与疾病无关的有机衰老的表现标志。对于这项调查，我们将对健康女性研究 (HWS) 的参与者进行横断面队列研究，这是一项以社区为基础的纵向队列研究，于 1983-84 年开始，刚刚获得退款以进行第四次风险决定因素检查围绝经期和绝经后妇女的因素变化。为了利用当前研究周期中 HWS 中获得的大量信息，我们将使用 Scheimpflug 摄影添加镜头透明度测量，该摄影使用线性密度测量来提供透明度的定量测量。验证晶状体透明度作为衰老的主要标志将使未来的研究人员能够将其用作揭示衰老过程的基准，并有可能作为人类干预研究的新型中间标志。 公共健康相关性：通过这项研究，我们的目的是确定晶状体透明度与心血管疾病和糖尿病（世界上发病率和死亡率的主要慢性病原因）测量值的关系，以及与白细胞端粒长度、白细胞介素 6 和白细胞介素 6 标记物的关系。身体和认知功能，从分子和整个有机体水平说明衰老。我们的结果将有助于验证晶状体透明度作为衰老、疾病、两者或两者都不是的主要标志；这一点很重要，因为衰老的主要标志物很少存在，而且也没有在体内进行测量，例如晶状体透明度，因此有可能更准确地反映衰老情况。确定晶状体透明度是否是衰老的主要标志将使未来的研究人员能够将其用作揭示衰老过程的基准，并可以作为测试衰老指标和调节剂的标准，以期优化衰老。