Stress and Immunosenescence: Protective Effects of Emotion Regulation

项目总结 确定影响老年人年龄相关免疫功能障碍(免疫衰老)的因素是 增进福祉和减少发病率的核心--这是一个日益严重的公共卫生问题，因为 不断扩大的老龄化人口。来自观察和实验研究的证据表明，压力是 与老年人的免疫功能较差有关。然而，人们对这一动态知之甚少 (个体内部变异性)压力影响老年人的情绪和生理机制 免疫功能。此外，情绪调节可能是一个保护因素，可以缓冲与压力有关的 免疫衰老在晚年发生，但这方面的知识还很匮乏。这份K99/R00提案奠定了 为独立研究职业奠定基础，专注于表征适应性情绪和 在应激状态下促进健康衰老的免疫机制。拟议的职业发展 计划将为应聘者提供：(1)老龄化研究理论和方法方面的专业知识，(2)高级 关于免疫衰老和与年龄相关的免疫变化的知识，以及(3)情绪和情绪训练 监管过程特别关注老龄化和压力的背景。指导阶段利用 肯塔基大学(英国)和 跨学科指导团队的专业知识(英国：Segerstrom博士和Lutz博士；加州大学伯克利分校：Mauss博士； 宾夕法尼亚州立大学：拉姆博士，加州大学洛杉矶分校：埃夫罗斯博士)。这些经验将补充候选人现有的 压力、情绪、健康和量化方法方面的背景。本研究有三个目的来检验 建议模型的不同组件。目标1(K99)：检查情绪调节是否缓和 生活应激源与免疫衰老的关系。目标2(K99)：解释日常压力源是如何 通过负面情绪的个体内变异性，与升高的压力生物标记物相关。目标3 (R00)：测试整个拟议的生物心理社会模型的缓和调解途径。这项研究 结合了一种严格的方法来测试建议的模型，方法是检查其交互组件 不同的时间域(即，多年来发生的生活压力源和更微观上发生的日常麻烦 在不同的样本(居住在社区的老年人和具有全国代表性的大样本)中 跨越免疫衰老的几个标记物(淋巴细胞衰老、炎症、主要促炎 转录因子，以及可能导致衰老的潜伏病毒)。并发和预期滞后 将使用多层建模和回归的调节和中介模型来测试关系 应激源中，对应激、免疫衰老和情绪的情绪和生理反应 监管。最终，这个项目将增加对压力源的动态机制的理解 对老年人免疫衰老的影响以及情绪调节在促进健康衰老中的作用。

PROJECT SUMMARY Identifying factors that influence age-related immune dysfunction (immunosenescence) in older adults is central to promoting well-being and reducing morbidity – an increasing public health concern given the rapidly expanding aging population. Evidence from observational and experimental studies suggests that stress is associated with poorer immune function in older adults. However, less is known about the dynamic (intraindividual variability) emotional and physiological mechanisms by which stress influences older adults' immune function. In addition, emotion regulation may be a protective factor that can buffer stress-related immunosenescence in later life, but there is a dearth of knowledge in this area. This K99/R00 proposal lays the foundation for an independent research career focused on characterizing adaptive emotional and immunological mechanisms that contribute to healthy aging during stress. The proposed career development plan will provide the candidate: (1) expertise in theories and methodologies of aging research, (2) advanced knowledge in immunosenescence and age-related immune changes, and (3) training in emotion and emotion regulation processes focused specifically on contexts of aging and stress. The mentored phase capitalizes on substantial research and professional development resources at the University of Kentucky (UK) and the expertise of an inter-disciplinary mentoring team (UK: Dr. Segerstrom and Dr. Lutz; UC Berkeley: Dr. Mauss; Penn State University: Dr. Ram, UCLA: Dr. Effros). These experiences will supplement the candidate's existing background in stress, emotions, health, and quantitative methods. The present study has three aims to test different components of a proposed model. Aim 1 (K99): To examine whether emotion regulation moderates the association between life stressors and immunosenescence. Aim 2 (K99): To explain how daily stressors are associated with elevated stress biomarkers, through intraindividual variability in negative emotion. Aim 3 (R00): To test the moderated mediation pathways of the entire proposed biopsychosocial model. The research incorporates a rigorous approach to test the proposed model by examining its interacting components across different time domains (i.e., life stressors that occur over years and daily hassles that occur on a more micro level), in various samples (community-dwelling older adults and a large, nationally representative sample), and across several markers of immunosenescence (lymphocyte senescence, inflammation, a chief proinflammatory transcription factor, and a latent virus that may drive senescence). Concurrent and prospective lagged moderation and mediation models using multilevel modeling and regression will be used to test relationships among stressors, emotional and physiological responses to stress, immunosenescence, and emotion regulation. Ultimately, this project will increase understanding of the dynamic mechanisms by which stressors influence immunosenescence in older adults and the role of emotion regulation in promoting healthy aging.