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所致的损伤或免疫系统的表现不佳。这种由年龄引起的免疫功能障碍可能在其他疾病状态中发挥隐藏作用，例如慢性炎症性疾病（慢性阻塞性肺病或类风湿性关节炎）和退行性疾病，例如动脉粥样硬化和骨关节炎。然而，缺乏系统性的努力来了解衰老对免疫机制的作用。这有两个原因。首先是缺乏一套明确的免疫学措施，这些措施易于执行但范围全面。一系列明确的此类测试（类似于肾功能或肝功能的测试）将允许人们表征不同环境下（包括老年、健康和疾病）的免疫功能状态（先天性、适应性甚至异常）。第二个原因是缺乏对普通人群衰老“正常”免疫生物学的理解。我们的建议有一个首要目标：开发并向其他研究人员提供对照健康受试者登记册和免疫特征数据库以及生物样本。存储库由至少 1100 名正常健康个体组成的队列开发而成。该数据集将包括对当地旧金山半岛 20 岁至 90 岁之间的一般人口（代表平等性别和代表性种族人口，以及按生命十年平均分配）的横断面分析。该注册表将包含人口统计数据、种族/民族、处方药、非处方药、维生素、替代疗法、身体功能问卷、替代联系人和 HIPPA 发布。将获得空腹血液用于免疫表型分析，如具体目标 3 中所述，免疫图谱将包含传统和新型免疫图谱测定的结果，以开发衰老的正常免疫图谱（使用 PBMC 子集分析、细胞因子和激活诱导的信号传导）。用于磷酸表位和基因表达分析的 PBMC）。这些分析的数据将有助于识别与衰老相关的正常免疫特征的生物标志物，以及与衰老表型方面的相关性，例如肌少症和残疾。这些受试者的免疫特征（以及正常的血液化学和人口统计数据）将可以作为未来纵向研究免疫谱随时间变化与衰老相关并发症的发展的基础。该提案的主要交付成果将是一个独特的开放获取电子数据存储库，其中包含多个尺度的表型信息（流行病学和临床，以及细胞和分子水平的免疫表型）以及遗传和蛋白质组信息（基因和蛋白质）对 1100 名 20 至 90 岁不同年龄的健康个体进行静息和激活 PBC 的表达）。该资源将使基于系统的衰老免疫学方法成为可能。 公共健康相关性：我们的提案是新成立的斯坦福大学免疫、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 7 十年生命中的免疫特征，其中包括对代表均匀分布的 1100 名正常个体进行横断面分析性别和年龄从 20 岁到 90 岁。将使用斯坦福人类研究所提供的仪器和技术从每个人获得人口统计数据和正常实验室化学成分以及他们的免疫特征免疫监测中心。我们将开发一个开放访问的数据存储库，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。