The VETSA Longitudinal Twin Study of Cortisol and Aging

描述(由研究人员提供)：压力和暴露于糖皮质激素(GC)水平升高会导致下丘脑-垂体-肾上腺(HPA)轴的变化，从而影响认知和适应性衰老。对压力的生理反应--包括皮质醇的升高--也受到心理社会和其他生物因素的个体差异的影响。确定与老龄化相关的风险和保护因素是公共卫生的优先事项。为此，我们将在一大批中年双胞胎的纵向评估中，通过唾液皮质醇测量来检查HPA对急性和持续应激源的反应，以及它与慢性应激源的相关性。对皮质醇的认知研究主要集中在海马区功能障碍和情景记忆。然而，在前额叶皮质和相关的执行功能中存在不成比例的年龄相关异常，并且在前额叶皮质中GC受体的浓度很高。我们认为，老年皮质醇相关的认知功能障碍将与执行功能和情景记忆缺陷有关。我们还将测量睾酮、脱氢表雄酮和GRK3基因的基因型。睾酮和脱氢表雄酮随年龄增长而下降，而皮质醇呈上升趋势；即使皮质醇不随年龄增长而增加，仍可表现出高皮质醇血症的症状。因此，皮质醇与脱氢表雄酮或睾酮的比率(而不是皮质醇的绝对水平)可能是功能性升高的有用指标。 皮质醇。GRK3在调节CRF受体中发挥作用；我们将研究GRK3的P-5变体是否与应激期间GC的高分泌和应激诱导反应的较低阈值有关。这项拟议的研究建立在我们由NIA资助的研究基础上，我们将其称为越南时代的双胞胎老龄化研究(VETSA)。Vetsa正在评估越南时代双胞胎登记处的720对双胞胎(360对在51岁+/-1岁；360对在56岁+/-1岁)，并计划每5年跟进一次。一项广泛的、为期一天的评估包括神经认知、个性/心理社会和健康/医学措施，以及用于基因分型的血液样本。关键的优势是从中年开始(在与年龄相关的大幅下降之前)，并且只有两个大的、狭窄的年龄段队列，可以最大限度地检测随着时间的推移个人内部的变化。这项研究将在Vetsa第三年开始，包括480对Vetsa双胞胎。我们将比较在家中和在实验室中的皮质醇、睾酮和脱氢表雄酮的测量，从而采用一种相对新颖的方法来提供与典型(在家)基础水平的比较。使用多变量双生分析方法，我们将确定遗传、共有和独特的环境因素对中年皮质醇的影响程度，以及它们与其他关键指标的关联。

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.