Energy-sensing Pathways, Healthy Aging and Longevity

描述(由申请人提供)：Kuakini医学中心(Kuakini)夏威夷Healthspan研究将集中一个由遗传学、流行病学和老年病科学家组成的多学科团队，使用创新的方法进行二级数据分析。我们将使用现有的人类数据和样本，来自长达45年的Kuakini檀香山心脏计划/檀香山亚洲老龄化研究，这是对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寿命的功能特征(“健康寿命”)，并将试图确定帮助人们健康地活到老年的遗传因素。虽然“成功”、“健康”或“有效”衰老等术语描述了一种慢性疾病最少的衰老模式，但人们对这种衰老的功能(生理和认知)、特征知之甚少，对遗传或环境预测因素也知之甚少。在最近的工作中，我们1)使用基于性能的功能测量方法对健康衰老的表型进行了操作；2)在一项纵向研究中确定了健康衰老和长寿的环境预测因素；3)发现了一个带有与健康衰老和长寿强烈相关的变异的基因(FOXO3a)；4)复制了CETP基因与长寿的关联，并将这一发现扩展到健康衰老。在目前的研究中，我们建议：1)使用来自能量感应通路的候选基因的两阶段嵌套病例对照研究和感兴趣区域周围的测序来识别与长寿相关的其他基因；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的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，可能会通过确定新疗法的生物靶点，对我们实现健康晚年的能力产生重大影响。我们的研究直接支持了NIA改善美国老年人健康和福祉的使命。 公共卫生相关性：Kuakini医学中心(Kuakini)夏威夷Healthspan研究将调查人们的基因如何影响他们实现健康晚年的能力。这项研究的重点是了解人的一生中的身体和认知功能，并确定使人们能够健康地活到特殊年龄的遗传和环境因素。对导致健康衰老的因素的研究可能有助于我们开发治疗方法，减少与年龄相关的疾病和残疾，并提高老年人的生活质量。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The Kuakini Medical Center (Kuakini) Hawaii Healthspan Study will investigate how people's genes affect their ability to achieve healthy old age. This study focuses on understanding physical and cognitive function over the lifespan and identifies genetic and environmental factors that enable people to survive to exceptional ages in good health. Research on factors that lead to healthy aging may help us develop therapies that result in less age-related disease and disability and increase quality of life at older ages.