Administrative Supplement for FOXO3 Genotype, InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III.

项目摘要 这是对父R 01奖项5 R 01 AG 027060 -10的补充：FOXO 3基因型，炎症老化， 心血管疾病和痴呆症。Kuakini夏威夷寿命研究III。母研究R 01拟 利用Kuakini檀香山心脏项目/Kuakini檀香山-亚洲老龄化研究（Kuakini HHP/Kuakini哈斯） 队列。Kuakini HHP研究始于1965年。AIM 1.进行FOXO 3基因型的前瞻性研究， 在成年期的大部分时间里，发病率和死亡率。假设：FOXO 3延长寿命超过 成年人的寿命主要是通过防止血管疾病。AIM 2.测试是否携带 长寿相关FOXO 3等位基因具有保护性抗炎血清谱。假设：FOXO 3 通过烟碱介导的抗炎途径降低死亡率。AIM 3.测试FOXO 3是否 基因型影响认知老化、AD和VCID。假设：促进长寿的基因变异也可能 促进健康的大脑老化，包括更好的认知功能，减少尸检时的大脑病理， AD和VCID的发生率。炎症可能是一个介导因素。家长奖是为了回应 PA-16-160：研究项目补助金（父R 01）。因此，重点不是新的数据收集。 对队列中年龄最大的成员（百岁老人）进行临床检查和生物标本收集， 但必须具有特殊价值。这将使世界上唯一真正纵向的百岁老人研究， 数据是在过去几十年中前瞻性收集的。这将优化我们的统计能力， 模型来评估FOXO 3基因如何影响活到特殊老年的能力，包括 炎症对长寿和健康衰老，特别是认知衰老的潜在作用。最有价值的 数据将来自这一特殊的纵向人类队列研究的其余成员。因此 本补充的目的是对约50名患者进行前所未有的55年随访临床检查。 Kuakini HHP/Kuakini哈斯研究的其余受试者（截至2020年1月1日，所有受试者均为百岁老人）， 测量额外的800种细胞因子，以将细胞因子随访延长至超过数十年的随访。 这解决了迫切需要检查我们的特别宝贵的最古老的幸存成员， 队列。对人类衰老研究至关重要，这种补充也将提供一种独特的资源， 目前还不存在，用于健康人类衰老的研究。它将提供足够的百岁老人的临床数据 以启动对百岁老人的首次纵向研究，从中年开始进行。

Project Summary This is a supplement to the parent R01 award 5R01AG027060-10: FOXO3 Genotype, InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III. The parent R01 study proposed to utilize the Kuakini Honolulu Heart Program/Kuakini Honolulu-Asia Aging Study (Kuakini HHP/Kuakini HAAS) cohort. The Kuakini HHP study began in 1965. AIM 1. CONDUCT a prospective study of FOXO3 genotype on incident disease and mortality across most of the adult lifespan. Hypothesis: FOXO3 enhances longevity over the adult lifespan principally through protection against vascular disease. AIM 2. TEST whether carriers of the longevity-associated FOXO3 allele have a protective anti- inflammatory serum profile. Hypothesis: FOXO3 reduces mortality through a cytokine-mediated anti-inflammatory pathway. AIM 3. TEST whether FOXO3 genotype influences cognitive aging, AD and VCID. Hypothesis: Gene variants that promote longevity may also promote healthy brain aging, including better cognitive function, less brain pathology on autopsy and lower rates of incident AD and VCID. Inflammation may be a mediating factor. The parent award was in response to PA-16-160: Research Project Grant (Parent R01). As such, the focus was not on new data collection. A clinical exam and bio-specimen collection on the oldest members of the cohort (centenarians) would, however, be of exceptional value. This would enable the world's only truly longitudinal centenarian study that has data prospectively collected over several prior decades. This would optimize the ability of our statistical models to assess how the FOXO3 gene influences the ability to live to exceptional old age including the potential role of inflammaging on longevity and healthy aging, particularly cognitive aging. The most valuable data would be from the remaining members of this exceptional longitudinal human cohort study. Therefore, the AIM of this supplement is to conduct an unprecedented 55-year follow-up clinical examination on the ~50 remaining participants of the Kuakini HHP/Kuakini HAAS study (all will be centenarians as of 1/1/2020) and measure an additional 800 cytokines to extend the cytokine follow-up to over a multi-decade follow-up. This addresses the need to urgently examine the oldest surviving members of our exceptionally valuable cohort. Of major importance to human aging research, this supplement will also provide a unique resource that does not currently exist, for studies of healthy human aging. It will provide clinical data on enough centenarians to enable the first longitudinal study of centenarians, conducted from mid-life.