Energy-sensing Pathways, Healthy Aging and Longevity

7.项目摘要 Kuakini医学中心（Kuakini）夏威夷Healthspan研究将集中一个多学科团队， 遗传学、流行病学和老年医学科学家关于使用创新方法获取二手数据的研讨会 分析.我们将使用现有的人类数据和标本从45年的库阿基尼檀香山心脏计划 /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在整个生命周期（“健康跨度”），并将 试图找出帮助人们健康长寿的遗传因素。 虽然诸如“成功”、“健康”或“有效”衰老的术语描述了具有最小的 慢性疾病，功能（身体和认知），这种衰老的特征知之甚少 对遗传或环境预测因子知之甚少。在最近的工作中，我们有1）操作化 健康老龄化的表型，使用基于性能的功能措施2）确定的环境 预测健康老龄化和长寿的纵向研究，3）发现一个基因（FOXO 3A）的变异 与健康衰老和长寿密切相关; 4）复制CETP基因与长寿相关 并将这一发现扩展到健康老龄化。 对于目前的研究，我们建议：1）使用两种方法鉴定与长寿相关的其他基因， 能量感应途径候选基因的阶段巢式病例对照研究和周围测序 感兴趣的领域; 2）对生存和健康生存的遗传预测因子进行前瞻性研究; 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。 发现影响疾病和残疾脆弱性的生物途径可能会产生巨大的影响 通过确定新疗法的生物靶点来实现健康老年的能力。我们的研究直接 支持NIA的使命，以改善美国老年人的健康和福祉。

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.