Clinical and Translational Core

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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.