Clinical and Translational Core

摘要 临床和翻译核心的总体目标是提供易于访问、现代化和 关于衰老的翻译研究的本地资源。最终，这将导致一个有价值和可持续的 生物医学研究社区的资源。项目负责人将能够评估与年龄相关的生物学 以及成人寿命的临床表型变化，利用前瞻性收集的数据集，来自 基因同质的种群。因此，研究人类的衰老过程将成为可能。 几十年--从中年到极老--通过查阅存档的生物标本和临床数据。 这种方法提供了比常见的对中间表型的短期研究的主要优势 衰老。它还消除了记忆偏见和其他在使用横断面或回溯性研究的研究中出现的偏见 收集的数据。 这个临床和翻译核心的中心假设是通过提供一个独特的生物信息库 和用于老龄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 在翻译衰老研究方面的教育和培训，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地老龄化。火奴鲁鲁库阿基尼医疗中心 心脏计划(Kuakini HHP)研究为正在进行的健康老龄化研究提供了一个独特的机会 对于大量的同质性研究人群，高质量的临床数据，长期的随访(五十二(52)年和 正在进行的)，大量非常年长、健康的人，以及大量收集的生物标本。还有，库阿基尼 医疗中心赞助并资助了一项正在进行的关于Kuakini HHP儿女的研究 在最近的Kuakini HHP后代研究中的队列。 临床和翻译核心对于收集、归档、管理和提供 生物谱学和临床数据，用于共同研究衰老。此核心旨在：(I)识别和 通过Kuakini HHP子孙研究招募800名参与者；(Ii)收集临床表型 关于健康和身体/认知功能以及血液、DNA、RNA和建立细胞系的信息； (3)检测两名Kuakini HHP男子的特定基因类型并评估其衰老表型(原始队列) 和Kuakini HHP后代研究(男性和女性的新后代队列)；和(Iv)提供项目 具有关于Kuakini HHP队列和Kuakini HHP的生物学、人口学和临床表型信息 后代研究。 以下目标支持临床和翻译核心的目标： 目标1：(A)收集关于健康和身体功能的生物学和临床表型信息 Kuakini HHP参与者的后代；和(B)向项目和档案提供这一信息 生物制品和临床数据，为未来的项目。我们建议招募一个分层随机抽样的800人 日裔美国人Kuakini HHP后代研究参与者(年龄40至90岁以上)。我们将过度抽样 长寿家庭并随机抽取平均寿命父母的后代样本，以优化老龄化- 相关结果。我们将收集人口统计、临床和认知信息，以及生物标本 当前和未来的项目。 目的2：对临床结果进行随访。临床结果包括疾病发作、残疾、 跟踪死亡率，并确定死因。 目的3：优化衰老研究的生物谱学和临床数据，协调数据管理。 我们建议：(I)利用DNA扩增，再生已故的Kuakini HHP男子的基因组 技术，并从20世纪70年代初开始储存血清。这将提供：(A)最大(n=~7000)和最长 (近50年)对老龄化结果队列的后续行动；(B)评估以下因素的影响的能力 关于从中年到死亡的衰老相关表型的遗传学；以及(C)显着增加统计能力； (2)Kuakini HHP男子和Kuakini HHP后代研究参与者(儿子和女儿) 长寿相关基因包括FOX03；(Iii)建立更多的淋巴母细胞系；(Iv)执行RNA Kuakini HHP后代研究参与者的测序；(V)从存储的数据中创造新的老化表型 用于连续测量大多数成人寿命中与衰老相关的表型变化的血液和组织 (40岁至100岁)，用于未来项目；(Vi)更新、合并和整合Kuakini HHP和其他Kuakini 将与老龄化有关的研究纳入一个共同的数据集；(7)管理对所有当前和未来项目的数据的获取， 编制用于统计分析的数据集，进行数据分析；()协助调查人员进行临床和 转换数据解释。

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.