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: 10022279
• 负责人: CATHLEEN S COLON-EMERIC
• 金额: $ 164.18万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10022279
• 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 procedures; 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; cell regeneration; clinical biomarkers; clinical care; cognitive function; cognitive recovery; cohort; design; education research; 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 cells; 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.

抽象的 主要协作的总体对象（物理弹性：指标和机制 老年人将表征特定的弹性表型，阐明生物学机制并验证 临床上有价值的预测工具和身体弹性的度量。该申请专注于弹性 三个对老年人整体健康中心的系统：肌肉骨骼，认知和免疫。 该应用的中心假设是对身体压力源的弹性受到生物学的影响 分子水平的机制。我们将检查与一个或多个相关的机制 七个“衰老支柱”，由Trans-Nih Geroscience兴趣组描述了，是A的 更广泛的恢复能力，可在多个压力源/响应方案中适用。一个间 来自老龄化研究人员的专业团队已组装以实现这些目标。团队 代表了六个由NIA资助的老年美国独立中心（OAIC）的专业知识，并利用其他 现有资源。主要协作团队将使用两步的方法。在第1阶段，工作组 将使用顺序的潜在类轨迹分析在现有数据集中定义特定的弹性表型 压力源后的结果度量。为其架构选择的三种弹性表型 与晚期健康状况以及我们团队的专业知识有关的是：骨科骨骼恢复后的骨质骨骼恢复 手术，感染后的免疫恢复以及手术/麻醉后的认知恢复。我们将进行飞行员 研究以识别与这些弹性相关的新型临床测试和生物标志物的研究。可行性和 试点研究的响应数据将为第2阶段的较大队列研究的设计提供信息。 第1阶段的月份，将选择最有希望的预测测试和标记，并将告知两个 第2阶段的平行活动。首先，接受选修手术的老年患者的纵向队列研究将 进行以验证更多样化的人群中的预测变量。第二阶段队列研究也将使我们能够 评估不同类型的预测因子（挑衅性测试，生理输出）之间的协同作用和相互作用 测量，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弹性确定基础的生物机制 模型以及体外人和小鼠肌管系统。这些模型系统适合干预 研究。第2阶段的生物学研究将旨在识别与一个或多个支柱有关的途径 衰老，以便它们可能支持多种类型的弹性，并建议治疗靶标和新颖， 弹性的干预措施。