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

FOXO3 基因型、炎症衰老、心血管疾病和痴呆。

• 批准号: 10622336
• 负责人: BRADLEY JOHN WILLCOX
• 金额: $ 42.12万
• 依托单位: KUAKINI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10622336
• 关键词: Address; Administrative Supplement; Adult; Age; Aging; Alleles; Anti-Inflammatory Agents; Asia; Asian Americans; Autopsy; Award; Biological Assay; Blood; Body mass index; Brain Pathology; COVID-19; Cardiovascular Diseases; Case-Control Studies; Chronic Disease; Cognitive aging; Cross-Sectional Studies; DNA amplification; Data; Data Collection; Dementia; Disease; Equipment; FOXO3A gene; Funding; Genes; Genotype; Glucose; Goals; Grant; Hawaii; Heart; Human; Impaired cognition; Inflammaging; Inflammation; Inflammatory; Interleukin-2; Japanese American; Longevity; Measurement; Measures; Mediating; Medical center; Modeling; Molecular; Outcome; Parents; Participant; Pathway interactions; Play; Population; Population Heterogeneity; Process; Prospective Studies; Publications; Reproducibility; Research Project Grants; Risk; Role; Sampling; Serum; Smoking; Smoking History; Study Subject; T-Lymphocyte; Testing; Time; TimeLine; Vascular Diseases; Work; age related; aging brain; cognitive function; cohort; cost; cytokine; disability; follow-up; functional decline; genetic variant; hazard; healthspan; healthy aging; inflammatory marker; longitudinal analysis; magnetic beads; men; mortality; mortality risk; programs; resilience; response; success

Project Summary This is a supplement to the parent R01 award 5R01AG027060-12: 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 utilizing 47 years of follow-up data. 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 and dementia. 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. Due to COVID-19 we had a number of delays in completing the primary Aims. For example, we had limited access to our medical center, which was in lock-down, we had supply chain disruptions, including delays in obtaining replacements for broken equipment, and inability to receive cytokine assay supplies in a timely manner. The AIM of this supplement is to complete the work that was disrupted due to COVID-19 issues and to measure an additional 600 study subjects (stored blood) for blood cytokine levels. The additional 600 study subjects will provide greater power to detect potentially statistically significant relations from currently underpowered borderline results. This supplement addresses the need to urgently examine scientific challenges surrounding healthy human aging, particularly with regard to inflammaging, a major driver of aging-related disease and disability.

项目摘要 这是父母R01奖5R01AG027060-12的补充：FOXO3基因型， 炎症，心血管疾病和痴呆症。 Kuakini Hawaii寿命研究III。这 父母R01研究提议利用Kuakini檀香山心脏计划/kuakini檀香山 - 亚洲 老化研究（Kuakini HHP/Kuakini Haas）队列。 Kuakini HHP研究始于1965年。目标1。 对使用47 多年的后续数据。假设：FOXO3在成年人的寿命中提高了寿命 通过保护血管疾病。目标2。测试长寿载体是否 相关的FOXO3等位基因具有保护性抗炎血清谱。假设：FOXO3 通过细胞因子介导的抗炎途径降低死亡率。目标3。测试是否 FOXO3基因型会影响认知衰老和痴呆。假设：基因变体 促进寿命也可能促进健康的大脑衰老，包括更好的认知功能，更少 大脑病理学对尸检和较低的事件AD和VCID率。炎症可能是 中介因子。父母奖是针对PA-16-160的回应：研究项目赠款（父母 R01）。因此，重点不是新数据收集。 由于COVID-19，我们完成了主要目标时有很多延误。例如，我们 我们有锁定的医疗中心的机会有限，我们有供应链 中断，包括延迟获得破损设备的替换，以及无法 及时接收细胞因子测定供应。该补充的目的是完成 由于199个问题而受到破坏的工作，并衡量了另外600个研究对象 （储存的血液）血细胞因子水平。额外的600个研究科目将提供更大的功率 从目前功能不足的边界结果中检测潜在具有统计学意义的关系。 这种补充是解决紧急检查健康科学挑战的必要性 人类衰老，特别是在炎症方面，是与衰老相关疾病的主要驱动力 残疾。

项目成果

Secrets of healthy aging and longevity from exceptional survivors around the globe: lessons from octogenarians to supercentenarians.

全球杰出幸存者的健康老龄化和长寿秘诀：八旬老人到超级百岁老人的教训。

• DOI: 10.1093/gerona/63.11.1181
• 发表时间: 2008
• 期刊: The journals of gerontology. Series A, Biological sciences and medical sciences
• 作者: Willcox,BradleyJ;Willcox,DCraig;Ferrucci,Luigi
• 通讯作者: Ferrucci,Luigi

Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa: controversies and clinical implications.

• DOI: 10.1097/mco.0000000000000019
• 发表时间: 2014-01
• 期刊: Current opinion in clinical nutrition and metabolic care
• 影响因子: 3.1
• 作者: Willcox BJ;Willcox DC
• 通讯作者: Willcox DC

Association analyses of insulin signaling pathway gene polymorphisms with healthy aging and longevity in Americans of Japanese ancestry.

日本裔美国人胰岛素信号通路基因多态性与健康衰老和长寿的关联分析。

• DOI: 10.1093/gerona/glt082
• 发表时间: 2014
• 期刊: The journals of gerontology. Series A, Biological sciences and medical sciences
• 作者: Morris,BrianJ;Donlon,TimothyA;He,Qimei;Grove,JohnS;Masaki,KamalH;Elliott,Ayako;Willcox,DCraig;Willcox,BradleyJ
• 通讯作者: Willcox,BradleyJ

FOXO3: A Major Gene for Human Longevity--A Mini-Review.

• DOI: 10.1159/000375235
• 发表时间: 2015
• 期刊: Gerontology
• 影响因子: 3.5
• 作者: Morris BJ;Willcox DC;Donlon TA;Willcox BJ
• 通讯作者: Willcox BJ

Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet.

• DOI: 10.1016/j.mad.2014.01.002
• 发表时间: 2014-03
• 期刊: Mechanisms of ageing and development
• 影响因子: 5.3
• 作者: Willcox DC;Scapagnini G;Willcox BJ
• 通讯作者: Willcox BJ