Characterizing Resiliencies to Physical Stressors in Older Adults: A Dynamical Physiological Systems Approach

项目摘要 当面对一个主要的身体压力源时，一些老年人能够恢复，下降幅度最小， 他们的身体和认知功能，而其他人遭受急剧的，不可逆转的功能下降。这是 弹性背后的核心概念。关于内在的（例如，生理和分子过程） 和外在的（例如，健康行为）影响弹性的因素。建议进行两阶段研究， 弥补我们理解上的差距。在第1阶段，将生成数据以描述年龄相关变化的特征 身体健康的决定因素和结果。第二阶段将涉及建设和验证 弹性的措施;其预测和临床价值的评估;和年龄相关的调查 生物学机制决定了特定的免疫力。 第1阶段具体目标： 1.定义，开发和完善弹性反应的表型措施，以三个预定义的物理 压力源：髋关节置换手术，血液透析和骨髓移植， 恶性血液病 2.制定和试点测试身体复原力的候选指标，包括静态和动态指标，以及 作为全球性的和针对具体压力源的措施。 3.确定复原力的前压力决定因素，包括疾病状态、心理社会 因子和分子测量，并表征其测量和统计特性。 4.综合目标1-3中开发的数据，为II期研究的设计提供信息。 第2阶段具体目标： 1.对于每一个待研究的临床压力源：建立和评价弹性评估， 第一阶段确定的措施。有前途的候选措施将进行交叉验证，其准确性， 预测短期和长期弹性应激反应的严格特征。相对预测 全局与特定、静态与动态、完全基于EHR与更广泛的弹性措施的价值 将被评估。 2.描述和评估与年龄相关的生物学机制，这些机制有助于恢复或缺乏恢复 这是具体到每一个临床压力，以及机制，是共同的三个具体 老年人的身体压力。 3.在准备进行干预研究时： 外部机构，并根据临床结果设计策略的试点研究，以加强依从性 和第一阶段确定的生物学机制。

Project Summary When confronted with a major physical stressor, some older adults are able to recover, with minimal decline, their physical and cognitive function, while others suffer precipitous, irreversible declines in function. This is the central notion behind resiliency. Little is known about the intrinsic (e.g., physiologic and molecular processes) and extrinsic (e.g., health behaviors) factors that impact resiliency. A two-phase study is proposed here to address this gap in our understanding. In phase 1, data will be generated to characterize age-related changes in physical resiliencies, their determinants, and their outcomes. Phase 2 will involve construction and validation of measures of resiliency; assessment of their predictive and clinical value; and investigation of age-related biological mechanisms determining specific resiliencies. Phase 1 Specific Aims: 1. To define, develop and refine phenotypic measures of resiliency responses to three pre-defined physical stressors: hip replacement surgery, initiation of hemodialysis, and bone marrow transplantation for hematologic malignancy. 2. To develop and pilot test candidate indicators of physical resiliency to include static and dynamic, as well as global and stressor-specific, measures. 3. To identify pre-stressor determinants of resilience, including measures of disease states, psychosocial factors, and molecular measures, and to characterize their measurement and statistical properties. 4. To synthesize data developed in Aims 1-3 to inform the design of Phase 2 studies. Phase 2 Specific Aims: 1. For each of clinical stressor to be studied: To build and evaluate assessments of resiliency incorporating measures identified in phase 1. Promising candidate measures will be cross-validated and their accuracy in predicting short- and long-term resilient stressor response rigorously characterized. The relative predictive value of global vs. specific, static vs. dynamic, and solely EHR-based versus broader resiliency measures will be assessed. 2. To characterize and assess age-related biological mechanisms that contribute to resilience or lack thereof that are specific to each clinical stressor, as well as mechanisms that are common across three specific physical stressors in older adults. 3. In preparation for the conduct of intervention studies: to cross-validate measures of resiliency at an external institution and to design pilot studies of strategies to bolster resiliencies based on clinical findings and biological mechanisms identified in Phase 1.