The VETSA Longitudinal Twin Study of Cortisol and Aging

VETSA 皮质醇与衰老的纵向双胞胎研究

• 批准号: 6950257
• 负责人: WILLIAM S. KREMEN
• 金额: $ 64.37万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6950257
• 关键词: G protein coupled receptor kinase; aging; apolipoprotein E; behavior prediction; clinical research; cognition; corticotropin releasing factor; cortisol; dehydroepiandrosterone; disease /disorder proneness /risk; gene environment interaction; genetic susceptibility; health behavior; hormone receptor; hormone regulation /control mechanism; human middle age (35-64); human subject; hypothalamic pituitary adrenal axis; longitudinal human study; male; mental health epidemiology; steroid hormone metabolism; stress; testosterone; twin /multiplet

DESCRIPTION (provided by investigator): Stress and exposure to elevated glucocorticoid (GC) levels cause changes in the hypothalamic-pituitary-adrenal (HPA) axis that affect cognitive and adaptive aging. Physiological responses to stress-including elevations in cortisol-are also moderated by individual differences in psychosocial and other biological factors. Identification of risk and protective factors associated with aging is a public health priority. Toward that end, we will examine HPA response to acute and sustained stressors, and its association with chronic stressors via salivary cortisol measures in the longitudinal assessment of a large sample of middle aged twins. Cognitive research on cortisol has focused on hippocampal dysfunction and episodic memory. However, there are disproportionate age-related abnormalities in prefrontal cortex and associated executive functions, and high concentrations of GC receptors in prefrontal cortex. We propose that cortisol-related cognitive dysfunction in aging will be associated with executive function as well as episodic memory deficits. We will also measure testosterone, DHEA, and genotype the GRK3 gene. Testosterone and DHEA decrease with age whereas cortisol tends to increase; even when cortisol does not increase with age, symptoms of hypercortisolemia may still be manifested. Thus, the ratio of cortisol to DHEA or testosterone (rather than absolute level of cortisol) may be a useful index of functionally elevated cortisol. GRK3 plays a role in regulating the CRF receptor; we will examine whether the P-5 variant of GRK3 is, associated with GC hypersecretion during stress and a lower threshold for stress-induced responses. The proposed study builds on our NIA-funded study, which we refer to as the Vietnam Era Twin Study of Aging (VETSA). The VETSA is assessing 720 twin pairs from the Vietnam Era Twin Registry (360 pairs at age 51+/-1; 360 pairs at age 56+/-1) with planned follow-up every 5 years. An extensive, daylong assessment includes neurocognitive, personality/psychosocial and health/medical measures, and blood samples for genotyping. Key advantages are beginning in midlife (before substantial age-related declines), and having only 2 large, narrow age cohorts to maximize power to detect within-person change over time. This study will begin in VETSA year 3 and include 480 VETSA twin pairs. We will compare at-home and in-lab cortisol, testosterone, and DHEA measures, thereby employing a relatively novel approach to provide comparison to typical (at-home) basal levels. Using multivariate twin analytic approaches, we will determine the extent of genetic, and shared and unique environmental factors influencing cortisol in midlife as well as their association with other key measures.

描述（由研究者提供）：压力和暴露于升高的糖皮质激素（GC）水平会导致影响认知和适应性衰老的下丘脑 - 垂体 - 肾上腺（HPA）轴的变化。对皮质醇的压力升高的生理反应也受到心理心理和其他生物学因素的个体差异的缓解。与衰老相关的风险和保护因素的识别是公共卫生的重点。为此，我们将检查HPA对急性和持续应激源的反应，及其与慢性压力源通过唾液皮质醇测量的纵向评估，以对大型中年双胞胎样本进行纵向评估。关于皮质醇的认知研究重点是海马功能障碍和情节记忆。但是，前额叶皮层和相关的执行功能中存在与年龄相关的异常，并且前额叶皮质中的GC受体高浓度。我们建议在老化中与皮质醇相关的认知功能障碍与执行功能以及情节记忆缺陷有关。我们还将测量GRK3基因的睾丸激素，DHEA和基因型。睾丸激素和DHEA随着年龄的增长而降低，而皮质醇倾向于增加；即使皮质醇随着年龄的增长而增加，高皮质血症的症状也可能仍表现出来。因此，皮质醇与DHEA或睾丸激素的比率（而不是绝对水平的皮质醇水平）可能是功能上升高的有用指数 皮质醇。 GRK3在调节CRF受体中起作用；我们将检查GRK3的P-5变体是否与应力期间的GC过度分泌有关，而应力诱导的响应的阈值较低。拟议的研究以我们的NIA资助研究为基础，我们将其称为越南时代的衰老研究（VETSA）。 VETSA正在评估越南时代双注册表的720双对（51岁+/- 1； 360对56岁+/- 1年），每5年进行了每5年的随访。一项广泛的日期评估包括神经认知，人格/社会心理和健康/医疗措施以及用于基因分型的血液样本。关键优势是在中年开始的（在与年龄相关的大幅下降之前），并且只有2个大，年龄狭窄的人群可以最大程度地发挥能力来检测随着时间的变化。这项研究将从3年级的Vetsa开始，并包括480个Vetsa双胞胎。我们将比较居家和利润内皮质醇，睾丸激素和DHEA测量方法，从而采用一种相对新颖的方法来与典型（家庭）基础水平进行比较。使用多元双胞胎分析方法，我们将确定影响中年皮质醇的遗传和独特环境因素的程度，以及它们与其他关键措施的关联。