Clinical and Translational Core

摘要 临床和翻译核心的总体目标是提供一个易于访问的，现代的， 本地资源，用于老龄化的转化研究。最终，这将带来一个有价值的、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 和临床表型的变化，在成人寿命，利用前瞻性收集的数据集，从一个 基因同质的群体因此，研究人类的衰老过程将是可能的。 从中年到极端老年-通过访问存档的生物标本和临床数据。 这种方法提供了主要的优势，超过普通的短期研究的中间表型， 衰老它还消除了回忆偏差和其他偏见中看到的研究，使用横截面或回顾性 收集的数据。 这个临床和转化核心的中心假设是，通过提供一个独特的生物储存库， 以及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， 教育和培训的转化老龄化研究，我们可以优化新的发现的机会， 新一代跨学科研究人员的健康老龄化。库阿基尼医疗中心檀香山 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， 对于大型同质研究人群，高质量的临床数据，长期随访（52年）， 正在进行中）、大量高龄健康人和大量生物标本收集。关于Kuakini 医学中心赞助并资助了一项正在进行的Kuakini HHP子女研究 最近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 生物样本和临床数据，用于衰老的合作研究。该核心旨在：（一）确定和 通过Kuakini HHP后代研究招募800名参与者;（ii）收集临床表型 关于健康和身体/认知功能信息，以及血液、DNA、RNA和已建立的细胞系; (iii)在两名Kuakini HHP男性（原始队列）中检测特定基因型并评估衰老表型 和Kuakini HHP后代研究（新的男女后代队列）;以及（iv）提供项目 Kuakini HHP队列和Kuakini HHP的生物学、人口统计学和临床表型信息 后代研究。 以下目标支持临床和翻译核心的目标： 目的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;以及（B）将此信息提供给项目和档案 生物标本和临床数据用于未来的项目。我们建议分层随机抽取800名 日本-美国Kuakini HHP后代研究参与者（年龄40至90岁以上）。我们会过度采样 长寿的家庭，并获得平均寿命的父母的后代的随机样本，以优化老化- 相关成果。我们将收集人口统计学、临床和认知信息以及生物标本， 当前和未来的项目。 目的2：对临床结局进行随访。临床结局包括疾病发作、残疾、 追踪死亡率和确定死亡原因。 目的3：优化衰老研究的生物标本和临床数据，协调数据管理。 我们建议：（i）利用DNA扩增技术再生Kuakini HHP男性死者的基因组 技术，和储存的血清从20世纪70年代初。这将提供：（a）最大（n= ~ 7 000）和最长的 （近五十年）随访队列的老龄化结果;（B）评估 （c）显著增加统计功效; (ii)基因型Kuakini HHP男性和Kuakini HHP后代研究参与者（儿子和女儿） 长寿相关基因，包括FOXO 3;（iii）建立额外的淋巴母细胞系;（iv）进行RNA 对Kuakini HHP后代研究参与者进行测序;（v）从储存的HHP基因中产生新的衰老表型。 用于连续测量大部分成年人寿命中与衰老相关的表型变化的血液和组织 (ages（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; ㈦管理所有当前和未来项目的数据访问， 为统计分析编制数据集，进行数据分析;以及（viii）协助研究者进行临床和 翻译数据解释。

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.