Clinical and Translational Core

临床和转化核心

• 批准号: 10015316
• 负责人: BRADLEY JOHN WILLCOX
• 金额: $ 84.31万
• 依托单位: KUAKINI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-10 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015316
• 关键词: Adult; Age; Aging; American; Archives; Biological; Biomedical Research; Blood; Blood specimen; Cardiovascular Diseases; Cause of Death; Center for Translational Science Activities; Cessation of life; Clinical; Clinical Data; Cognitive; Cohort Studies; Collection; Communities; DNA; DNA amplification; Data; Data Analyses; Data Set; Daughter; Dementia; Diabetes Mellitus; Disease; FOXO3A gene; Family; Funding; Future; Generations; Genes; Genetic; Genome; Genotype; Goals; Health; Heart; Human; Japanese American; Japanese Population; Longevity; Longitudinal cohort study; Malignant Neoplasms; Measurement; Medical center; Mental Depression; Modernization; Natural regeneration; Onset of illness; Outcome; Parents; Parkinson Disease; Participant; Persons; Phenotype; Physical Function; Population; Process; RNA; Research; Research Personnel; Resources; Sampling; Serum; Son; Specimen; Statistical Data Interpretation; Technology; Testing; Tissues; Training and Education; Update; Whole Blood; Woman; age related; biobank; biomedical resource; clinical phenotype; cognitive function; cohort; data management; design; disability; established cell line; follow-up; healthy aging; lymphoblastoid cell line; men; middle age; mortality; novel; offspring; phenotypic data; programs; prospective; recruit; study population; transcriptome sequencing; translational study

ABSTRACT The overall objective of the Clinical and Translational Core is to provide an easily accessible, modern, and local resource for translational studies of aging. Ultimately, this will result in a valuable and sustainable resource for the biomedical research community. Project leaders will be able to assess age-related biological and clinical phenotypic changes over the adult lifespan, utilizing a prospectively collected dataset, from a genetically homogeneous population. Thus, it will be possible to study the aging process in humans over decades – from middle age to extreme old age – by accessing archived biological specimens and clinical data. This approach provides major advantages over commonplace short-term studies of intermediate phenotypes of aging. It also eliminates recall bias and other bias seen in studies which use cross-sectional or retrospectively collected data. The central hypothesis for this Clinical and Translational Core is that by providing a unique biorepository and clinical dataset for aging studies, the expertise to manage and share such data, and opportunities for education and training in translational aging research, we can optimize opportunities for novel discoveries for healthier aging by a new generation of interdisciplinary investigators. The Kuakini Medical Center Honolulu Heart Program (Kuakini HHP) studies provide a unique opportunity for ongoing research on healthy aging due to the large homogeneous study population, high quality clinical data, long, follow-up (fifty-two (52) years and ongoing), large number of very old, healthy persons, and large collection of biospecimens. Also, Kuakini Medical Center has sponsored and funded an ongoing study of the sons and daughters of the Kuakini HHP cohort in the recent Kuakini HHP Offspring Study. The Clinical and Translational Core is crucial for collecting, archiving, managing, and providing biospecimens and clinical data for collaborative studies on aging. This Core is designed to: (i) Identify and recruit 800 participants through the Kuakini HHP Offspring Study; (ii) Collect clinical phenotypic information on health and physical/cognitive function, as well as blood, DNA, RNA, and establish cell lines; (iii) Test for specific genotypes and assess phenotypes of aging in both Kuakini HHP men (original cohort) and Kuakini HHP Offspring Study (new offspring cohort of men and women); and (iv) Provide the Projects with biological, demographic and clinical phenotypic information on the Kuakini HHP cohort and Kuakini HHP Offspring Study. The following aims support the goals of the Clinical and Translational Core: AIM 1: (a) Collect biological and clinical phenotypic information on health and physical functions from offspring of Kuakini HHP participants; and (b) Provide this information to the Projects and archive biospecimens and clinical data for future projects. We propose to recruit a stratified random sample of 800 Japanese-American Kuakini HHP Offspring Study participants (ages 40 to 90+ years). We will oversample families with longevity and obtain a random sample of offspring of average-lived parents to optimize aging- related outcomes. We will collect demographic, clinical and cognitive information, and biospecimens for current and future projects. AIM 2: Conduct follow-up for clinical outcomes. The clinical outcomes include onset of diseases, disability, tracking of mortality, and ascertainment of cause of death. AIM 3: Optimize biospecimen and clinical data for aging research and coordinate data management. We propose to: (i) Regenerate the genome of decedent Kuakini HHP men, utilizing DNA amplification technology, and stored serum from the early 1970s. This will provide: (a) The largest (n= ~7,000) and longest (almost five decades) follow-up of a cohort for aging outcomes; (b) The ability to assess the influence of genetics on aging-related phenotypes from middle age to death; and (c) Markedly increase statistical power; (ii) Genotype Kuakini HHP men and Kuakini HHP Offspring Study participants (sons and daughters) for longevity-related genes including FOXO3; (iii) Establish additional lymphoblastoid cell lines; (iv) Perform RNA Sequencing on Kuakini HHP Offspring Study participants; (v) Create novel aging phenotypes from stored blood and tissue for serial measurement of aging-related phenotypic change over most of the adult lifespan (ages 40s to 100s) for future projects; (vi) Update, merge and integrate the Kuakini HHP and other Kuakini aging-related studies into a common dataset; (vii) Manage access to data for all current and future projects, program datasets for statistical analyses, conduct data analysis; and (viii) Assist investigators with Clinical and Translational data interpretation.

抽象的 临床和转化核心的总体目标是提供易于访问，现代和 衰老翻译研究的本地资源。最终，这将导致有价值且可持续的 生物医学研究界的资源。项目负责人将能够评估与年龄有关的生物学 以及使用前瞻性收集的数据集中，成人寿命的临床表型变化， 遗传均质人群。那就是可以研究人类的衰老过程 数十年（从中年到极端年龄），通过访问存档的生物标本和临床数据。 这种方法比普通的短期研究提供了主要优势。 老化。它还消除了在使用横截面或回顾性的研究中看到的召回偏见和其他偏见 收集的数据。 该临床和转化核心的中心假设是通过提供独特的生物座 以及用于老化研究的临床数据集，管理和共享此类数据的专业知识以及机会 转化衰老研究中的教育和培训，我们可以优化新发现的机会 新一代跨学科研究人员更健康的衰老。 Kuakini医疗中心檀香山 心脏计划（Kuakini HHP）研究为正在进行的健康衰老的研究提供了一个独特的机会 对于大型同质研究人群，高质量的临床数据，长时间的随访（52（52）年和 正在进行的），大量非常老的，健康的人和大量的生物测量。另外，Kuakini 医疗中心赞助并资助了对Kuakini HHP儿子和女儿的持续研究 在最近的Kuakini HHP后代研究中，队列。 临床和翻译核心对于收集，归档，管理和提供至关重要 用于衰老的合作研究的生物测量和临床数据。该核心旨在：（i）识别和 通过Kuakini HHP后代研究招募800名参与者； （ii）收集临床表型 有关健康和身体/认知功能以及血液，DNA，RNA和建立细胞系的信息； （iii）测试两位Kuakini HHP男性（原始同类）的特定基因型和评估表型 和Kuakini HHP后代研究（男女的新后代队）； （iv）提供项目 有关Kuakini HHP队列和Kuakini HHP的生物，人口统计和临床表型信息 后代研究。 以下目的支持临床和转化核心的目标： 目标1：（a）从健康和身体功能中收集生物学和临床表型信息 Kuakini HHP参与者的后代； （b）将此信息提供给项目和档案 未来项目的生物测量和临床数据。我们建议募集800的分层随机样本 日裔美国人Kuakini HHP后代研究参与者（40至90岁以上）。我们将过度采样 具有长寿的家庭，并获取平均寿命的后代随机样本，以优化衰老 相关结果。我们将收集人口，临床和认知信息，以及生物测量 当前和未来的项目。 AIM 2：进行临床结果的随访。临床结果包括疾病的发作，残疾， 跟踪死亡率和确定死亡原因。 AIM 3：优化用于老化研究并协调数据管理的生物测量和临床数据。 我们建议：（i）使用DNA扩增再生死者Kuakini HHP男性的基因组 技术，并储存了1970年代初期的血清。这将提供：（a）最大（n = 〜7,000）和最长 （将近五十年）对衰老结果的后续行动； （b）评估影响的能力 从中年到死亡的与衰老相关的表型的遗传学； （c）显着增加统计能力； （ii）基因型Kuakini HHP男子和Kuakini HHP后代研究参与者（儿子和女儿） 寿命相关的基因，包括FoxO3； （iii）建立其他淋巴母细胞系； （iv）执行RNA 对Kuakini HHP后代研究参与者进行排序； （v）从存储中创建新颖的衰老表型 在大多数成人寿命中 （40至100岁）未来项目； （vi）更新，合并和整合Kuakini HHP和其他Kuakini 与衰老相关的研究中的研究集； （vii）管理所有当前和未来项目的数据访问， 用于统计分析的程序数据集，进行数据分析； （viii）协助研究人员进行临床和 翻译数据解释。