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.

抽象的 PRIME 合作的总体目标（身体复原力：指标和机制） 老年人）的目的是表征特定的恢复表型，阐明生物学机制并验证 具有临床价值的预测工具和身体恢复力的测量该应用程序侧重于恢复力。 对老年人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。 该应用的中心假设是，对物理压力源的恢复力受到生物的影响 我们将研究分子水平上的机制是否与一种或多种相关。 跨 NIH 老年科学兴趣小组描述的七个“衰老支柱”构成了 适用于多种压力源/反应场景的更通用的恢复能力。 为了实现这些目标，我们组建了由老龄化研究人员组成的专业团队； 代表来自 NIA 资助的六个美国老年人独立中心 (OAIC) 的专业知识，并利用其他 PRIME 协作团队将在第一阶段采用工作组的方法。 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 压力源后的结果测量 三种复原力表型，根据其总体情况进行选择。 与晚年健康的相关性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、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志物。 试点研究的反应数据将为第二阶段更大的队列研究的设计提供信息。在最后的 6 在第一阶段的几个月中，将选择最有希望的预测测试和标记，并将通知两个 第二阶段的并行活动。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进行预测因子的验证 第二阶段队列研究也将使我们能够 评估不同类型预测因子之间的协同作用和相互作用（激发测试、生理输出 其次，不同类型的恢复力（肌肉骨骼、认知、免疫）。 将利用新开发的小鼠恢复力来确定支撑恢复力的生物机制 模型，以及体外人类和小鼠肌管系统，这些模型系统适合干预。 第二阶段的生物学研究将旨在确定与一个或多个支柱相关的途径。 衰老使它们可能支撑多种类型的复原力，并提出治疗目标和新颖的、 增强复原力的干预措施。