Energy-sensing Pathways, Healthy Aging and Longevity

7.项目摘要 库阿基尼医疗中心(Kuakini)夏威夷Healthspan研究将集中一个多学科团队 遗传学、流行病学和老年学科学家关于使用创新方法获取二次数据的研究 分析。我们将使用现有的人类数据和45年的Kuakini火奴鲁鲁心脏计划的样本 /檀香山亚洲老龄化研究，日裔美国男性老龄化和慢性病的纵向研究。 我们的工作将集中在健康老龄化的功能特征上(健康寿命)并将 尝试找出帮助人们健康长寿的遗传因素。 而诸如“成功的”、“健康的”或“有效的”衰老等术语则描述了一种最小限度的衰老范式 慢性疾病，这种衰老的功能(生理和认知)特征，人们知之甚少 人们对遗传或环境预测因子知之甚少。在最近的工作中，我们已经实现了 使用基于性能的功能测量的健康衰老的表型2)确定的环境 健康衰老和长寿的预测因素在一项纵向研究中，3)发现了一个带有变异的基因(FOXO3a 与健康衰老和长寿密切相关；4)复制了CETP基因与长寿的关联 并将这一发现扩展到健康的衰老。 在目前的研究中，我们建议：1)使用两个基因来识别与长寿相关的其他基因 能量敏感通路候选基因的阶段性嵌套病例对照研究及周围测序 感兴趣的领域；2)对生存和健康生存的遗传预测因素进行前瞻性研究；3) 对主要衰老相关性状变化率的遗传预测因子进行前瞻性研究。 影响疾病和残疾易感性的生物途径的发现可能会产生巨大的影响 关于我们通过确定新疗法的生物靶点来实现健康晚年的能力。我们的研究直接 支持NIA改善美国老年人健康和福祉的使命。

7. Project Abstract The Kuakini Medical Center (Kuakini) Hawaii Healthspan Study will focus a multidisciplinary team of genetic, epidemiological, and geriatric scientists on the use of innovative approaches for secondary data analysis. We will use existing human data and specimens from the 45-year Kuakini Honolulu Heart Program /Honolulu Asia Aging Study, longitudinal studies of aging and chronic diseases in Japanese-American men. Our work will focus on functional characteristics of healthy aging over the lifespan ("healthspan") and will attempt to identify genetic factors that help people survive to older ages in good health. While terms such as "successful", "healthy" or "effective" aging describe a paradigm of aging with minimal chronic disease, the functional (physical and cognitive), characteristics of such aging are poorly understood and little is known about genetic or environmental predictors. In recent work we have 1) Operationalized phenotypes of healthy aging that use performance-based measures of function 2) Identified environmental predictors of healthy aging and longevity in a longitudinal study, 3) Found a gene (FOXO3A) with variants strongly associated with healthy aging and longevity; 4) Replicated the CETP gene association with longevity and extended the finding to healthy aging. For the current study, we propose to: 1) IDENTIFY additional genes associated with longevity using a two stage nested case-control study of candidate genes from energy sensing pathways and sequencing around areas of interest; 2) CONDUCT a prospective study of genetic predictors of survival and healthy survival; 3) CONDUCT a prospective study of genetic predictors of rate of change in major aging related traits. Discovery of biologic pathways that affect vulnerability to disease and disability could have a dramatic impact on our ability to achieve healthy old age by identifying biological targets for new therapies. Our study directly supports NIA's mission to improve the health and well-being of older Americans.