Lifespan Effects of Biologically Embedded Stress on Health

 描述（由申请人提供）：本K 08提案的目的是为Lewina Lee博士提供必要的专业知识，以开展独立的研究职业生涯，调查生物，心理和行为因素的相互作用，这些因素是压力与年龄之间的关联。由Avron Spiro博士领导的指导团队（波士顿大学; BU），Laura Kubzansky博士在几位顾问的协助下，李博士将由美国哈佛大学的教授和宾夕法尼亚州立大学的教授大卫阿尔梅达（David Almeida）指导李博士开展拟议的研究和培训活动。基于李博士在临床衰老和定量方法学方面的背景，培训计划将使她能够：（1）获得人类应激反应生理学方面的培训;（2）提高她对年龄相关疾病的病理生理过程的认识;（3）获得领导独立研究项目的技能。主要培训活动包括正式课程和教学法;跨学科专家的指导;研究设计、数据收集和分析方面的实践培训;以及出席会议。培训将在BU和PSU进行。培训活动通过实施一项指导性研究计划得到加强。拟议研究的目标是检查异常急性应激反应和多系统生理失调的机制，解释累积的心理社会压力暴露对心血管疾病和过早死亡的负面影响。具体目标是：（1）将急性应激反应作为累积心理社会压力暴露与多系统生理失调之间关联的中介进行检查;（2）将20年来生理功能的年龄轨迹作为累积心理社会压力暴露与晚年健康之间关联的中介进行检查。这些目标将通过分析多模态数据从全国代表性的中年在美国的研究和纵向数据从VA规范老化研究使用结构方程模型。拟议研究的意义在于：（a）更准确地了解心理社会压力暴露的累积影响“深入皮肤”影响整个生命周期的身体健康的生物机制，以及（B）确定“急性压力反应的风险特征，表明与压力相关的负面健康结果的早期风险。该项目直接涉及NIA关于发现与老年人疾病和残疾有关的原因和风险因素的战略方向（A-1）。预计研究结果将为制定干预措施提供信息，以减少晚年的疾病负担（战略方向B-1）。这 该奖项将使李博士具备深入的知识和技能，领导一个独立的跨学科研究计划，以调查整个生命周期中压力与健康之间的机械联系。

 DESCRIPTION (provided by applicant): The objective of this K08 proposal is to provide Dr. Lewina Lee with the necessary expertise to launch an independent research career investigating the interplay of biological, psychosocial, and behavioral factors that underlie the association between stress and health over age. A mentoring team, led by Avron Spiro, Ph.D. (Boston University; BU), Laura Kubzansky, Ph.D. (Harvard University), and David Almeida (Pennsylvania State University; PSU), with assistance from several consultants, will guide Dr. Lee in conducting the proposed research and training activities. Building on Dr. Lee's background in clinical aging and quantitative methodology, the Training Plan will allow her to: (1) obtain training in the physiology of human stress response; (2) advance her knowledge of pathophysiologic processes that underlie age-related diseases; and (3) gain skills to lead an independent research program. Key training activities include formal coursework and didactics; mentorship from interdisciplinary experts; hands-on training in study design, data collection and analysis; and conference attendance. Training will take place at BU and PSU. Training activities are augmented by implementing a mentored Research Plan. The goal of the proposed research is to examine abnormal acute stress response and multisystem physiologic dysregulation as mechanisms that explain the negative effects of cumulative psychosocial stress exposure on cardiovascular disease and premature mortality. The Specific Aims are to: (1) examine acute stress response as a mediator of the association between cumulative psychosocial stress exposure and multisystem physiologic dysregulation; and (2) examine age trajectories of physiological functioning over 2 decades as mediators of the association between cumulative psychosocial stress exposure and later-life health. These aims will be addressed by analyzing multi-modal data from the nationally representative Midlife in the United States study and longitudinal data from the VA Normative Aging Study using structural equation models. The significance of the proposed research lies in: (a) a more precise understanding of the biological mechanisms by which the cumulative impact of psychosocial stress exposure "gets under the skin" to affect physical health across the lifespan, and (b) the identification of a "risky profile of acute stress response that signals early risk for stress-related negative health outcomes. This project directly addresses NIA's strategic direction (A-1) on discovering causes and risk factors associated with disease and disability in older adults. Findings are expected to inform the development of interventions to reduce disease burden in later life (strategic direction B-1). This award will equip Dr. Lee with in-depth knowledge and skills to lead an independent and interdisciplinary research program to investigate the mechanistic links between stress and health across the lifespan.