Immunobiology of Aging

衰老免疫生物学

• 批准号: 8046604
• 负责人: CHARLES GARRISON FATHMAN
• 金额: $ 349.55万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8046604
• 关键词: Address; Adult; Affect; Age; Aging; Alternative Therapies; Atherosclerosis; B-Lymphocyte Subsets; B-Lymphocytes; Bioinformatics; Biological; Biological Assay; Biological Markers; Biometry; Blood; Blood Chemical Analysis; Cell Count; Cells; Cessation of life; Chemistry; Chronic; Chronic Obstructive Airway Disease; Clinical; Communities; Comorbidity; Cross-Sectional Studies; Cytokine Activation; Data; Data Analyses; Data Collection; Data Set; Databases; Degenerative Disorder; Degenerative polyarthritis; Dendritic Cells; Development; Disease; Epidemiology; Ethnic Origin; Event; Fasting; Flow Cytometry; Frequencies; Future; Gender; Gene Expression; Gene Proteins; General Population; Genetic; Guidelines; Health; Hepatic; Homeostasis; Human; Immune; Immune System Diseases; Immune system; Immunity; Immunobiology; Immunologic Monitoring; Immunology; Impairment; Individual; Infection; Inflammatory; Institutes; Kidney; Kinetics; Length; Life; Lipids; Longitudinal Studies; Malignant Neoplasms; Measures; Metabolic; Molecular; Natural Immunity; Online Systems; Performance; Peripheral Blood Mononuclear Cell; Persons; Pharmaceutical Preparations; Phenotype; Physical Function; Population; Predisposition; Proteomics; Questionnaires; Race; Registries; Relative (related person); Research Personnel; Resources; Rest; Rheumatoid Arthritis; Role; Sampling; San Francisco; Scientist; Serum; Signal Pathway; Signal Transduction; Specimen; Staining method; Stains; Stem cells; System; T-Lymphocyte; Technology; Testing; Time; Transplantation; University Hospitals; Vitamins; abstracting; age related; base; chemokine; cohort; cytokine; disability; electronic data; functional status; healthy aging; high risk; instrumentation; monocyte; neutrophil; normal aging; novel; open source; population based; protein expression; regenerative; repository; sarcopenia; telomere; tool

DESCRIPTION (provided by applicant): The immune system is profoundly affected by aging. Older individuals are at higher risk of death and disability from infections and cancer. The reason for such disproportionate susceptibility appears to be age-attributed impairment or suboptimal performance of immune system. Such age-attributed immune dysfunction might have a hidden role in other disease states such as chronic inflammatory diseases (COPD or rheumatoid arthritis) and degenerative diseases such as atherosclerosis and osteoarthritis. Yet, systematic efforts to understand the role of aging on immunological mechanisms are lacking. There are two reasons for this. The first is absence of well-defined set of immunological measures that are easy to perform but comprehensive in scope. A well-defined battery of such tests, similar to those for renal or hepatic function, would allow one to characterize the functional status of immunity (innate, adaptive or even aberrant) in varied settings including old age, health and disease. The second reason is the absence of understanding of what constitutes 'normal' immunobiology of aging in the general population Our proposal would have one overriding aim: To develop and make available to other investigators a control healthy subject registry and immune profile database and bio-specimen repository developed from a cohort of at least 1100 normal healthy individuals. The dataset will comprise a cross-sectional analysis of the local San Francisco Peninsula general population between the ages of 20 and 90 (representing equal gender and representative ethnic population, and equal distribution by decade of life). The registry will contain demographic data, race/ethnicity, prescribed medications, over the counter medications, vitamins, alternative therapies, physical function questionnaire, alternative contact person, and HIPPA release. Fasting blood will be obtained for immune phenotyping as described in Specific Aim 3 the immune profile will contain the results of both conventional and novel immune profiling assays to develop the normative immune profile of aging (using PBMC subset analysis, cytokines, and activation induced signaling of PBMCs for phosphoepitope and gene expression analyses). Data from these analyses will be useful in identifying biomarkers of the normal immune profile associated with aging as well as correlation with phenotypic aspects of aging such as sarcopenia and disability The immune profile (as well as normal blood chemistries and demographic data) of these subjects will be made available to serve as the basis for future longitudinal study of change in the immune profile over time in association with the development of co-morbidities associated with aging. The primary deliverable for this proposal will be a unique open access electronic data repository that has phenotypic information in multiple scales (epidemiological, and clinical, and, at the cell and molecular level, of immune phenotype) and genetic and proteomic information (gene and protein expression of resting and activated PBCs) on 1100 healthy individuals at different ages from 20 to 90 years. This resource will enable a systems-based approach to the immunology of aging. PUBLIC HEALTH RELEVANCE: Our proposal is an initiative of the new Stanford Institute of Immunity, Transplantation and Infection (ITI) to develop an immune profile of normal healthy subjects throughout 7 decades of life consisting of a cross sectional analysis of 1100 normal individuals representing equal distribution of gender and from age 20 to 90. Demographic data and normal lab chemistries will be obtained from each individual as well as their immune profile using instrumentation and technology available in the Stanford Human Immune Monitoring Center. We will develop an open-access data repository that will enable free sharing of high throughput analyte data and appropriately de-identified phenotypic data on a web-based platform using high quality open source and statistical tools.

描述（由申请人提供）：免疫系统受衰老的深刻影响。老年人患死亡和癌症的死亡和残疾风险更高。这种不成比例的敏感性的原因似乎是年龄归因于免疫系统的障碍或次优性能。这种年龄属性的免疫功能障碍可能在其他疾病状态中具有隐藏的作用，例如慢性炎性疾病（COPD或类风湿关节炎）和退化性疾病，例如动脉粥样硬化和骨关节炎。然而，缺乏了解衰老对免疫机制的作用的系统努力。有两个原因。首先是没有定义明确的免疫学措施，这些措施易于执行但在范围上进行全面。在包括老年，健康和疾病在内的各种环境中，类似于肾脏或肝功能的电池定义明确的电池，类似于肾脏或肝功能的电池。第二个原因是缺乏了解普通人群中衰老的“正常”免疫生物学的理解，我们的建议将具有一个压倒性的目标：开发并使其他研究人员可以控制健康的受试者注册表和免疫概况数据库和免疫特征数据库以及由至少1100个正常健康的健康人群开发的。该数据集将对20至90岁的旧金山半岛一般人口进行横断面分析（代表同等的性别和代表性的种族人口，以及在生命十年之前的分布）。注册表将包含人口统计数据，种族/民族，处方药，柜台药物，维生素，替代疗法，身体功能问卷，替代联系人和HIPPA释放。如特异性目标3所述，将获得空腹血液以进行免疫表型，免疫特征将包含常规和新型免疫分析测定法的结果，以发展衰老的规范性免疫特征（使用PBMC子集分析，细胞因子，激活和激活诱导PBMC的磷pepitope和Gene表达分析的信号）。来自这些分析的数据将有助于确定与衰老相关的正常免疫特征的生物标志物以及与衰老的表型相关的相关性，例如肌肉细胞减少症和残疾人，这些受试者的免疫特征（以及正常的血液化学和人口统计学数据）将可用于与未来的较长范围相关的范围，以使其与范围内的发展相关。该提案的主要可交付方式将是一个独特的开放访问电子数据存储库，其表型信息具有多个尺度（流行病学和临床，在细胞和分子水平，免疫表型的细胞和分子水平，遗传和蛋白质组学信息（基因和蛋白质）信息（基因和蛋白质和蛋白质的静止和活性pbc的蛋白质表达），在1100个健康的eges中，来自20至90年的不同年龄。该资源将使基于系统的衰老免疫学方法。 公共卫生相关性：我们的提案是新的斯坦福大学免疫，移植和感染研究所的举措免疫监测中心。我们将开发一个开放访问数据存储库，该数据存储库能够使用高质量的开源和统计工具在基于Web的平台上免费共享高吞吐量分析物数据，并在基于Web的平台上适当地识别表型数据。