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）：免疫系统受到衰老的深刻影响。老年人因感染和癌症而死亡和残疾的风险更高。这种不成比例的易感性的原因似乎是年龄引起的损伤或免疫系统的次优性能。这种年龄归因的免疫功能障碍可能在其他疾病状态中具有隐藏的作用，如慢性炎症性疾病（COPD或类风湿性关节炎）和退行性疾病，如动脉粥样硬化和骨关节炎。然而，缺乏系统的努力来理解衰老对免疫机制的作用。原因有二。首先是缺乏一套明确的免疫措施，这些措施易于执行，但范围广泛。类似于肾功能或肝功能的一系列明确的此类测试将允许人们表征包括老年、健康和疾病在内的各种环境中的免疫功能状态（先天性、适应性或甚至异常）。第二个原因是缺乏对一般人群中衰老的“正常”免疫生物学的理解。我们的建议有一个压倒一切的目标：开发并向其他研究人员提供一个对照健康受试者登记处和免疫概况数据库以及从至少1100名正常健康个体的队列中开发的生物标本库。该数据集将包括对当地弗朗西斯科半岛20至90岁的一般人群（代表平等的性别和代表性的种族人口，以及按十年寿命的平等分布）的横断面分析。登记研究将包含人口统计学数据、人种/种族、处方药、非处方药、维生素、替代疗法、身体功能调查问卷、替代联系人和HIPPA放行。将采集空腹血液进行免疫表型分析，如特定目标3所述，免疫特征将包含常规和新型免疫特征分析试验的结果，以开发衰老的标准免疫特征（使用PBMC亚群分析、细胞因子和PBMC的活化诱导信号传导进行磷酸化表位和基因表达分析）。来自这些分析的数据将可用于鉴定与衰老相关的正常免疫谱的生物标志物以及与衰老的表型方面（如肌肉减少症和残疾）的相关性。（以及正常的血液化学和人口统计学数据）这些受试者中的50%将作为未来纵向研究的基础，研究免疫特征随时间的变化与发展的关系。与衰老有关的并发症。该提案的主要可交付成果将是一个独特的开放获取电子数据存储库，其中包含多个尺度（流行病学、临床以及细胞和分子水平的免疫表型）的表型信息以及遗传和蛋白质组信息（静息和激活的PBCs的基因和蛋白质表达）关于1100名20至90岁不同年龄段的健康个体。这一资源将使一个系统为基础的方法来衰老的免疫学。 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（ITI）的一项倡议，旨在开发正常健康受试者在70年生命中的免疫概况，包括对1100名正常个体的横截面分析，这些个体代表性别和年龄从20岁到90岁的平等分布。将使用斯坦福大学人类免疫监测中心提供的仪器和技术，从每个个体获得人口统计学数据和正常实验室化学品以及其免疫特征。我们将开发一个开放获取的数据库，使用高质量的开源和统计工具，在基于网络的平台上免费共享高通量分析物数据和适当去识别的表型数据。