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: 7265214
• 负责人: WILLIAM S. KREMEN
• 金额: $ 53.47万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7265214
• 关键词: 1 year old; ADRBK2 gene; Acute; Address; Adrenal Cortex Hormones; Adrenal Glands; Adult; Affect; Age; Age-Years; Aging; Alcohol or Other Drugs use; Alcohols; American; Anabolic steroids; Apolipoprotein E; Arts; Attention; Back; Bereavement; Biological; Biological Assay; Biological Factors; Blood; Blood Pressure; Blood specimen; Boston; Cardiovascular system; Characteristics; Chronic; Cigarette; Cognition; Cognitive; Cognitive aging; Collection; Condition; Consumption; Corticotropin-Releasing Hormone Receptors; Daily; Data; Data Collection; Data Set; Development; Diet Habits; Early identification; Elderly; Elevation; Environment; Environmental Risk Factor; Episodic memory; Equation; Exposure to; Family; Flying body movement; Functional disorder; Funding; Future; Genes; Genetic; Genotype; Glucocorticoid Receptor; Glucocorticoids; Health; Health Priorities; Hippocampus (Brain); Home environment; Hormones; Human Resources; Hydrocortisone; Hypertension; Hypothalamic structure; Impaired cognition; Individual; Individual Differences; Investigation; Laboratories; Life Stress; Link; Longitudinal Studies; Lung; Mails; Measures; Mediating; Medical; Memory; Memory impairment; Mental Depression; Mental Health; Methods; Military Personnel; Modeling; Motor; Multivariate Analysis; Neurocognitive; Numbers; Outcome; Output; Parents; Performance; Personality; Persons; Pharmaceutical Preparations; Phenotype; Physical activity; Physiological; Pituitary Gland; Play; Prefrontal Cortex; Preventive; Prospective Studies; Psychosocial Factor; Public Health; Quantitative Genetics; Rate; Recording of previous events; Registries; Regulation; Relative (related person); Research; Research Personnel; Retirement; Risk; Risk Factors; Role; Saliva; Salivary; Sampling; Sensory; Services; Site; Spouses; Stress; Structure; Symptoms; Syndrome; Testing; Testosterone; Time; Time Study; Twin Multiple Birth; Twin Studies; Variant; Vietnam; age effect; age related; allostatic load; base; biological adaptation to stress; brain volume; cardiovascular risk factor; caregiving; cognitive function; cohort; coping; cost; day; dehydroepiandrosterone; depressive symptoms; executive function; experience; follow-up; genetic association; hypercortisolemia; hypothalamic-pituitary-adrenal axis; indexing; interest; men; middle age; novel strategies; programs; prospective; psychosocial; response; sample collection; self esteem; social; steroid hormone; stressor; tool

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）：应激和暴露于糖皮质激素（GC）水平升高导致下丘脑-垂体-肾上腺（HPA）轴变化，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调节。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，我们将研究HPA对急性和持续的压力源的反应，以及它与慢性压力源通过唾液皮质醇的措施，在一个大样本的中年双胞胎的纵向评估。皮质醇的认知研究主要集中在海马功能障碍和情景记忆。然而，在前额皮质和相关的执行功能中存在不成比例的与年龄相关的异常，并且在前额皮质中存在高浓度的GC受体。我们认为，皮质醇相关的认知功能障碍在老龄化将与执行功能以及情节记忆缺陷。我们还将测量睾酮、脱氢表雄酮和GRK 3基因的基因型。睾酮和脱氢表雄酮随着年龄的增长而减少，而皮质醇往往增加;即使皮质醇不随年龄的增长而增加，高皮质醇血症的症状仍然可能表现出来。因此，皮质醇与DHEA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GRK 3在调节CRF受体中起作用;我们将研究GRK 3的P-5变体是否与应激期间GC分泌过多和应激诱导反应的较低阈值相关。这项拟议的研究建立在我们的NIA资助的研究基础上，我们将其称为越南时代双胞胎衰老研究（VETSA）。VETSA正在评估越南时代双胞胎登记处的720对双胞胎（360对年龄为51+/-1; 360对年龄为56+/-1），计划每5年进行一次随访。一个广泛的，为期一天的评估包括神经认知，个性/心理社会和健康/医疗措施，和血液样本的基因分型。关键优势是从中年开始（在与年龄相关的大幅下降之前），并且只有2个大的，狭窄的年龄组，以最大限度地提高检测随时间推移的人内变化的能力。本研究将开始于VETSA第3年，纳入480对VETSA双胞胎。我们将比较在家里和在实验室的皮质醇，睾酮和脱氢表雄酮的措施，从而采用一种相对新颖的方法来提供比较典型的（在家里）的基础水平。使用多变量双胞胎分析方法，我们将确定影响中年皮质醇的遗传、共享和独特环境因素的程度，以及它们与其他关键指标的关联。

项目成果

Role of CRF receptor signaling in stress vulnerability, anxiety, and depression.

• DOI: 10.1111/j.1749-6632.2009.05011.x
• 发表时间: 2009-10
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Hauger RL;Risbrough V;Oakley RH;Olivares-Reyes JA;Dautzenberg FM
• 通讯作者: Dautzenberg FM

Carboxyl-terminal and intracellular loop sites for CRF1 receptor phosphorylation and beta-arrestin-2 recruitment: a mechanism regulating stress and anxiety responses.

CRF1 受体磷酸化和 β-arrestin-2 募集的羧基末端和细胞内环位点：调节压力和焦虑反应的机制。

• DOI: 10.1152/ajpregu.00099.2006
• 发表时间: 2007
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Oakley,RobertH;Olivares-Reyes,JAlberto;Hudson,ChristineC;Flores-Vega,Fabiola;Dautzenberg,FrankM;Hauger,RichardL
• 通讯作者: Hauger,RichardL