Physical Resiliencies: Indicators and Mechanisms in the Elderly Collaborative

摘要 PRIME协作（身体复原力：指标和机制， 老年人）是为了表征特定弹性表型，阐明生物学机制，并验证 临床上有价值的预测工具和身体恢复力的测量。该应用程序侧重于恢复能力， 这三个系统对老年人的整体健康至关重要：肌肉骨骼、认知和免疫。的 本申请的中心假设是，对身体压力源的恢复力受到生物学因素的影响， 分子水平的机制。我们将研究是否与一个或多个 七个“衰老的支柱”，这已被描述的trans-NIH老年科学兴趣小组，基础是一个 更普遍的恢复能力，适用于多种压力源/反应情景。一个间- 为了实现这些目标，已经组建了一支由老龄化研究人员组成的专业团队;该团队 代表了来自六个国家情报局资助的美国老年人独立中心（OAIC）的专业知识，并利用其他 现有资源。PRIME协作团队将采用两阶段方法。在第一阶段，工作组 将使用序列的潜在类轨迹分析来定义现有数据集中的特定弹性表型。 压力源之后的结果测量。这三种弹性表型，选择他们的过度膨胀， 与晚年健康相关的以及我们团队的专业知识，是：骨科手术后的肌肉骨骼恢复 手术、感染后的免疫恢复和手术/麻醉后的认知恢复。我们将进行试点 研究以确定与这些疾病中的每一种相关的新的临床测试和生物标志物。可行性和 来自初步研究的反应数据将为II期更大队列研究的设计提供信息。在决赛中6 在第一阶段的几个月里，将选择最有希望的预测性测试和标志物，并将告知两个 第二阶段的平行活动。首先，对接受择期手术的老年患者进行纵向队列研究， 在更多样化的人群中验证预测因子。2期队列研究还将使我们能够 评估不同类型的预测因子（激发试验、生理输出）之间的协同作用和相互作用 措施，生物标志物）和不同类型的弹性（肌肉骨骼，认知，免疫）。第二、 将使用新开发的小鼠复原力来确定支撑复原力的生物学机制 模型和体外人和小鼠肌管系统。这些模型系统适用于干预 问题研究II期生物学研究将旨在确定与一个或多个支柱相关的途径， 老化，使他们有可能巩固多种类型的弹性，并提出治疗目标和新的， 加强服从的干预措施。

ABSTRACT The overarching objectives of the PRIME Collaborative (Physical Resilience: Indicators and Mechanisms in the Elderly) are to characterize specific resilience phenotypes, elucidate biological mechanisms, and validate clinically valuable predictive tools and measures of physical resilience. The application focuses on resilience in three systems that are central to older adults' overall health: musculoskeletal, cognitive, and immune. The central hypothesis of this application is that resilience to physical stressors is influenced by biological mechanisms at the molecular level. We will examine whether mechanisms associated with one or more of the seven “Pillars of Aging,” which have been described by the trans-NIH Geroscience Interest Group, underlie a more generalized capacity for recovery that applies across multiple stressor/response scenarios. An inter- professional team of aging researchers from has been assembled to accomplish these objectives; the team represents expertise from six NIA-funded Older American Independence Centers (OAICs) and leverages other existing resources. The PRIME Collaborative team will use a two-phased approach. In Phase 1, workgroups will define specific resilience phenotypes in existing datasets using latent class trajectory analysis of sequential outcome measures following a stressor. The three resilience phenotypes, selected for their over-arching relevance to late life health as well as our team's expertise, are: musculoskeletal recovery after orthopedic surgery, immune recovery after infection, and cognitive recovery after surgery/anesthesia. We will conduct pilot studies to identify novel clinical tests and biomarkers associated with each of these resiliencies. Feasibility and response data from pilot studies will inform the design of a larger cohort study in Phase 2. In the final 6 months of Phase 1, the most promising predictive tests and markers will be selected and will inform two parallel activities in Phase 2. First, a longitudinal cohort study of older patients undergoing elective surgery will be conducted to validate predictors in a more diverse population. The Phase 2 cohort study will also allow us to assess synergy and interactions between different types of predictors (provocative tests, physiologic output measures, biomarkers) and different types of resilience (musculoskeletal, cognitive, immune). Second, biological mechanisms underpinning resilience will be identified using newly developed mouse resilience models, and in vitro human and mouse myotubule systems. These model systems are suitable for intervention studies. The Phase 2 biological studies will be designed to identify pathways related to one or more Pillars of Aging so that they are likely to underpin multiple types of resilience, and suggest therapeutic targets and novel, resilience-bolstering interventions.