Extracellular Vesicle Analyses to Develop Aging and Resilience Biomarkers

细胞外囊泡分析以开发衰老和弹性生物标志物

• 批准号: 10550122
• 负责人: Virginia Kraus
• 金额: $ 60.63万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10550122
• 关键词: Address; Age; Aging; Antigen-Presenting Cells; Autophagocytosis; Baltimore; Behavior; Biological Markers; Biological Models; Biological Process; Biology; Blood; Body Fluids; Cardiovascular system; Cell Aging; Cell model; Cells; Chondrocytes; Clinical; Cohort Studies; Collaborations; Communication; Complex; Data; Data Set; Defect; Elderly; Exercise; Fibroblasts; Fluorescence; Funding; Funding Opportunities; Goals; Health; Hematopoietic stem cells; Hip Fractures; Hip region structure; Homeostasis; Human; Immune; Immune system; In Vitro; Individual; Inflammaging; Inflammation; Interleukin-6; Knowledge; Laboratories; Literature; Longevity; Mammalian Cell; Measures; Mediating; Mediator; Metabolic; Methodology; Methods; MicroRNAs; Microscopic; Mitochondria; Mus; Myocardial Ischemia; Natural Killer Cells; Nucleic Acids; Operative Surgical Procedures; Organism; Outcome; Oxidative Stress; PECAM1 gene; Parents; Participant; Patients; Phenotype; Physical Performance; Physical activity; Physiological; Plasma; Play; Population; Process; Production; Proteins; Proteome; RNA; Randomized; Recovery; Regenerative capacity; Regulation; Reperfusion Injury; Resolution; Resources; Role; Sampling; Serum; Sorting; Specimen; Surface; Testing; Tissues; United States National Institutes of Health; Validation; Vesicle; Video Microscopy; WI 38 cell; age related; aged; cell type; cohort; cytokine; data de-identification; epidemiology study; exercise intensity; exercise training; extracellular vesicles; follow-up; healthy aging; immune function; immunoregulation; immunosenescence; improved; insulin sensitivity; interest; milliliter; mode of exercise; muscle metabolism; nanoparticle; particle; peripheral blood; predictive marker; promote resilience; resilience; responders and non-responders; response; secondary analysis; senescence; specific biomarkers; stem cells; stressor; trafficking; vesicular release

Abstract Extracellular vesicles (EVs) are membranous particles released from nearly all cell types into all bodily fluids evaluated to date — including serum and plasma. Depending on tissue of origin, health state and organism age, they carry a variety of complex cargo consisting of nucleic acids, proteins and metabolites. Although resilience at a tissue level has largely been attributed to stem cells, recent evidence increasingly points to their production of EVs as mediators of their remarkable regenerative capacity. The rapid release of small EVs is induced by physical activity and believed to contribute to the long-term beneficial effects of regular exercise on muscle metabolism, the cardiovascular system as well as immune modulation. The goal of this project is to develop biomarkers of aging and resilience through analyses of EVs. Due to their coordinate regulation of tissue homeostasis and biological processes through intercellular trafficking of microRNA and protein cargo, EVs are particularly attractive for this project because they can potentially serve as DIRECT biomarkers of aging and resilience, namely indicators AND mediators of the aging process and response to stressors. We will use our newly developed 18-channel-high-resolution flow cytometric methodology with validation by nanoparticle tracking video microscopy, and fluorescence-activated particle sorting that we have established in the laboratory to evaluate our large existing extensive human sample sets (n=4213 individuals from EPESE, PALS, STRRIDE, BHS and the Duke 1KP (1000 Patient) cohort) with associated deidentified data and longitudinal follow-up (6 months to 23 years). We have preliminary data demonstrating an age-related decline in specific subsets of circulating EVs. We also have identified that a subset of EVs, including some of those declining with age, are induced with exercise training and predict a beneficial metabolic response to exercise. These data, together with our collaborators for this project, bring together extensive expertise in aging, resilience, exercise, and physical performance across the lifespan (ages 18 to 102 years). These resources and capabilities provide a unique opportunity for us to significantly advance EVs along a biomarker pipeline and to identify effectors of heathy aging and resilience. For this reason, we are responding to the funding Opportunity Announcement PA-17-088 that invites applications that employ secondary analysis of existing data sets or stored biospecimens to address clinically related issues on aging changes influencing health across the lifespan.

抽象的 细胞外蔬菜（EV）是从几乎所有细胞类型释放到所有体液中的膜颗粒 迄今为止评估 - 包括血清和血浆。取决于起源，健康状态和生物的组织 年龄，它们携带各种复杂的货物，这些货物由核酸，蛋白质和代谢产物组成。虽然 在组织水平上的弹性很大程度上归因于干细胞，最近的证据越来越指向其 生产电动汽车作为其显着再生能力的介体。小电动汽车的快速释放是 由体育锻炼引起，并被认为有助于定期锻炼的长期有益作用 肌肉代谢，心血管系统以及免疫调节。这个项目的目标是 通过分析电动汽车来开发衰老和弹性的生物标志物。由于其协调法规 组织稳态和生物学过程通过微细胞贩运microRNA和蛋白质货物， 电动汽车对该项目特别有吸引力，因为它们可以作为直接生物标志物 衰老和韧性，即衰老过程的指标和介体以及对压力源的反应。我们将 使用我们新开发的18通道高分辨率流式细胞术方法，并通过 纳米颗粒跟踪视频显微镜以及我们已经在 评估我们现有大型人类样本集的实验室（n = 4213个来自Epese的人， PALS，Strride，BHS和杜克1KP（1000名患者），并具有相关的DEDIATIFIDED数据和 纵向随访（6个月至23年）。我们有初步数据证明了与年龄有关的下降 在循环电动汽车的特定子集中。我们还确定了一个电动汽车的子集，包括其中一些 随着年龄的增长，运动训练会引起诱导，并预测对运动的有益代谢反应。 这些数据以及我们的合作者为该项目提供了广泛的衰老专业知识， 整个生命周期（18至102岁）的韧性，运动和身体表现。这些资源 功能为我们提供了一个独特的机会 并确定希西衰老和弹性的影响。因此，我们正在回应资金 机会公告PA-17-088邀请申请员工对现有数据的辅助分析 集合或存储的生物测量，以解决有关临床上有关衰老变化的临床问题的影响 寿命。