The Genetic Basis of a Disease Free Model of Aging

描述（由申请人提供）： 有关参与或介导人类衰老速度的遗传因素的信息有限。这些信息对于我们理解衰老过程中个体变异的生物学非常有价值，这可以帮助我们理解长寿的机制，并对改善个体的健康寿命产生影响。这方面的一个重要问题是缺乏足够的疾病独立的衰老生物标志物来定义为表型。该探索性项目的目的是从基于遗传的研究的角度评估利用透镜透明度的正常下降作为疾病无关的衰老模型的可行性。本探索性评估的目的是确定可行性、基本原理和研究设计细节，这些细节将用于为一系列研究提供依据，这些研究将涉及使用疾病无关的衰老模型识别参与人类衰老过程和衰老过程速率的基因和基因-环境相互作用。为了实现这一探索性项目的目标，将从多代家庭收集定量透镜透明度测量、健康、暴露和人口统计数据以及DMA。每个家庭的先证者将从正在进行的基于人群的研究中招募，心血管健康研究（CHS）是一项在65岁及以上成人中进行的基于人群的纵向研究。来自活跃CHS参与者的初步数据表明，他们愿意联系他们的家庭成员参与涉及衰老遗传学的研究，大多数人的家庭结构将有利于进行这项探索性研究，并且大约一半的活跃参与者的原始透镜都完好无损，可用于测量。这是第一项研究提出使用透镜透明度作为人类衰老过程的连续定量测量，适用于遗传连锁和基因鉴定。

DESCRIPTION (provided by applicant): Information is limited about the genetic factors participating in or mediating the pace of aging in humans. Such information would be valuable to our understanding of the biology of individual variation in the aging process, which could help us understand the mechanisms of longevity and have an impact on improving the health span of individuals. A significant problem in this regard is the lack of adequate disease independent biomarkers of aging to define as phenotypes. The aims of this exploratory project will assess the feasibility of utilizing the normal decline in lens transparency as a disease independent model of aging from the perspective of a genetic based study. The aims of this exploratory assessment will establish the feasibility, rationale, and research design details that v/ill be utilized to inform the basis for a line of investigation that will involve identifying gene(s) and gene-environment interactions that participate in the aging process and rate of the aging process in humans using a disease independent model of aging. To accomplish the goals of this exploratory project, quantitative lens transparency measurements, health, exposure and demographic data, and DMA will be collected from multigenerational families. The proband for each family will be recruited from an ongoing population based study, the Cardiovascular Health Study (CHS), which is a population based longitudinal study being conducted in adults aged 65 and older. Preliminary data from active CHS participants indicates that they are willing to contact their family members to participate in a study involving the genetics of aging, the majority have family structures that will be conducive to conducting this exploratory study, and that approximately half of the active participants will have both of their original lens intact and available for measurement. This is the first study to propose to use lens transparency as a continuous, quantitative measure of the human aging process that will be suitable for genetic linkage and gene identification.