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

项目摘要 当面临主要的身体压力时，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 弹性背后的核心理念。对内在的(例如，生理和分子过程)知之甚少 以及影响复原力的外在因素(如健康行为)。这里提出了一项分两个阶段的研究 解决我们理解中的这一差距。在第一阶段，将生成数据来表征与年龄有关的变化 在身体复原力、其决定因素和结果方面。第二阶段将涉及构建和验证 复原力测量；评估其预测和临床价值；以及与年龄相关的调查 决定特定复原力的生物机制。 阶段1的具体目标： 1.定义、开发和改进对三种预定义物理特性的弹性响应的表型测量 应激源：髋关节置换手术、开始血液透析和骨髓移植 恶性血液病。 2.制定和试行物理复原力的候选指标，将静态和动态也包括在内 作为全球性的和特定于应激源的措施。 3.确定影响复原力的压力前决定因素，包括疾病状态、心理社会因素 因子和分子量度，并表征它们的量度和统计特性。 4.综合在AIMS 1-3中开发的数据，为第二阶段研究的设计提供信息。 阶段2的具体目标： 1.对于每一种待研究的临床应激源：建立和评估复原力评估 第一阶段确定的措施。有希望的候选措施将进行交叉验证，其准确性将在 预测短期和长期的弹性应激源反应具有严格的特征。相对预测性 全球与特定、静态与动态、仅基于EHR与更广泛的恢复力指标的价值 将会被评估。 2.确定和评估与年龄有关的生物机制，这些机制有助于或缺乏复原力 针对每个临床应激源，以及在三个特定的 老年人的身体压力源。 3.为开展干预研究做准备：交叉验证在 外部机构，并根据临床结果设计增强复原力战略的先导性研究 以及在第一阶段中确定的生物机制。

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.