Physical Resiliencies: Indicators and Mechanisms in the Elderly Collaborative

身体弹性：老年人协作的指标和机制

• 批准号: 10247066
• 负责人: CATHLEEN S COLON-EMERIC
• 金额: $ 121.9万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247066
• 关键词: Acute; Aging; American; Anesthesia procedures; Area; Attention; Biological; Biological Markers; Biological Models; Characteristics; Clinical; Cognitive; Cohort Studies; Connecticut; Consensus; Data; Data Set; Development; Discipline; Elderly; Epigenetic Process; Experimental Models; Frequencies; Funding; Genetic; Geroscience; Health; Human; Immune; In Vitro; Infection; Inflammation; Inflammatory; Injury; Institution; Interest Group; Intervention; Intervention Studies; Laboratories; Laboratory Study; Longitudinal Studies; Longitudinal cohort study; Maryland; Measurement; Measures; Metabolic; Metabolism; Modeling; Molecular; Mus; Muscle; Musculoskeletal; Operative Surgical Procedures; Orthopedic Surgery; Outcome; Outcome Measure; Output; Pathway interactions; Pattern; Pharmacology; Phase; Phenotype; Physiological; Pilot Projects; Population Heterogeneity; Predictive Value; Prospective Studies; Recovery; Research Personnel; Research Support; Resources; Stress; System; Testing; United States National Institutes of Health; age related; base; biomarker identification; care delivery; clinical biomarkers; clinical care; cognitive function; cognitive recovery; cohort; design; education research; feasibility testing; forest; immune function; improved; lifestyle intervention; member; mouse model; novel; older patient; postoperative recovery; predictive marker; predictive test; predictive tools; programs; ranpirnase; resilience; response; skills; stem cell self renewal; stressor; synergism; systematic review; therapeutic target; working group

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.

摘要 Prime Collaborative的总体目标(身体复原力： 老年人)是为了表征特定的恢复力表型，阐明生物学机制，并验证 具有临床价值的预测工具和身体复原力的测量。该应用程序侧重于在 对老年人的整体健康至关重要的三个系统：肌肉骨骼系统、认知系统和免疫系统。这个 这一应用的中心假设是，对物理应激源的恢复能力受到生物因素的影响 分子水平上的机制。我们将检查与一个或多个 由跨NIH老年科学兴趣小组描述的七个“老龄化支柱”构成了 更普遍的恢复能力，适用于多个应激源/应对方案。一位内部人士- 为了实现这些目标，已经组建了由年长的研究人员组成的专业团队；该团队 代表NIA资助的六个较老的美国独立中心(OAIC)的专业知识，并利用其他 现有资源。Prime Collaborative团队将使用两个阶段的方法。在第一阶段，工作组 将使用序列的潜在类轨迹分析在现有数据集中定义特定的弹性表型 紧跟应激源后的结果测量。三种韧性表型，因其突出的拱形而被选中 与晚年健康和我们团队的专业知识相关的是：骨科术后的肌肉骨骼恢复 手术、感染后的免疫恢复以及手术/麻醉后的认知恢复。我们将进行试点 研究以确定与这些弹性相关的新的临床测试和生物标记物。可行性和 来自试点研究的反应数据将为第二阶段更大规模的队列研究的设计提供信息。 在第一阶段的几个月里，将选出最有希望的预测性测试和标记，并将为两个 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的纵向队列研究将 在更多样化的人群中进行预测以验证预测因素。第二阶段队列研究还将使我们能够 评估不同类型的预测因素(刺激测试、生理输出)之间的协同作用和相互作用 生物标记物)和不同类型的复原力(肌肉骨骼、认知、免疫)。第二, 将使用新开发的小鼠弹性来确定支持弹性的生物机制 模型，以及体外人和小鼠的肌管系统。这些模型系统适合于干预 学习。第二阶段的生物学研究将被设计成确定与一个或多个 衰老，使它们可能支持多种类型的弹性，并建议治疗目标和新颖的， 增强韧性的干预措施。