Exceptional survival and longevity in New England

描述(由申请人提供)：到目前为止的研究表明，异常长寿(EL)和特定的特殊存活(ES)表型是家族性的，并表明这种熟悉性的一个重要组成部分是遗传。曾被认为过于复杂的环境、行为、遗传和随机因素的谜题，EL和可能相关的ES 表型似乎与许多可识别和有影响的因素有关。 这个拟议的特殊家庭生存研究中心的抽样框架将是一个基于人口的样本，即生活在马萨诸塞州和康涅狄格州的达到EL的个人，定义为男性年龄=98岁，女性年龄100岁。这些LLI代表了在20世纪之交出生的队列中年龄最大的1%的成员。根据我们目前每年招收700名适龄受试者的能力、额外资源的提供，以及我们以往一项以人口为基础的较小规模研究的经验，我们将在这个5年计划的3年招募期内招收809名土地注册机构、806名兄弟姐妹和692名土地注册机构的后代。由于这是一项基于种群的研究，我们将能够根据特定的特征估计该地区的LLI产量、同胞和后代以及存活率。联邦医疗保险和最低数据集(MDS)数据将由联邦医疗保险和医疗补助服务中心提供，以帮助衡量人口普查名单的敏感性和登记集合的代表性，调查地区和全国范围内的联邦医疗保险利用率和LLI中的MDS数据，以便生成候选ES表型并增强登记受试者的表型数据。我们观察到，百岁老人的兄弟姐妹经历了从20岁到极老的出生队列中一半的死亡率。EIO、Kestenbaum和他的同事的研究支持了这一假设，即与童年有关的重要事件在获得EL的能力中发挥着重要作用。这项拟议工作的一部分将专门用于进一步调查这些因素。在较高年龄时，特定的ES表型可以代表相对的生存优势，我们将同时在LLI的后代中进行研究，并根据表型的不同，在LLI中回顾或同时进行研究。将使用以家庭为基础的分析方法来调查家庭聚集性和传播方式的EL和ES表型。通过将LLI及其家庭成员纳入基于人群的样本，并作为MCS-ESF的一个组成部分进行表型和分析工作，我们将能够以一种有助于数据和未来遗传物质共享的方式来研究这些罕见的家族，测试样本框架的重复性，以及远远超过任何一项单独研究本身所能实现的智力努力。

DESCRIPTION (provided by applicant): Research thus far indicates that exceptional longevity (EL) and specific exceptional survival (ES) phenotypes are familial and suggests that a significant component of that familiality is genetic. Once thought to be much too complex a puzzle of environmental, behavioral, genetic and stochastic factors, EL and likely associated ES phenotypes appear to be likely associated with a number of discernable and influential factors. The sampling frame for this proposed Exceptional Survival in Families Study Center will be a population-based sample of individuals achieving EL, defined as males age >= 98 years and females age >100 years, living in Massachusetts and Connecticut. These LLIs represent the 1% oldest members of the cohort born around the turn of the 20th century. Based upon our current ability to enroll 700 age-validated subjects per year, the provision of additional resources and our experience with a previous smaller population-based study, we will enroll 809 LLIs, 806 siblings and 692 offspring of LLIs during the 3 year recruitment period of this 5 year project. Since this is a population-based study, we will be able to estimate for this region, the yield of LLIs, sibships and offspring as well as survivorship according to specific traits. Medicare and Minimum Data Set (MDS) data will be provided by the Centers for Medicare and Medicaid Services to help gauge sensitivity of the census lists and representativeness of the enrolled set, to investigate regional and nationwide Medicare utilization and MDS data among LLIs in order to generate candidate ES phenotypes and to augment phenotypic data on enrolled subjects. We have observed that siblings of centenarians experience half the mortality of their birth cohort from age 20 up through extreme old age. Work by EIo, Kestenbaum and colleagues supports the hypothesis that there are important childhood related events that play significant roles in the ability to achieve EL. A portion of this proposed effort will be dedicated to further investigating such factors. At older ages, a relative survival advantage could be typified by specific ES phenotypes which we shall investigate concurrently among offspring of LLIs and retrospectively or concurrently, depending upon the phenotype, among LLIs. Family-based analytic approaches will be used to investigate EL and ES phenotypes for familial aggregation and modes of transmission. By enrolling LLIs and their family members in a population-based sample and conducting a phenotyping and analytic effort as an integral component of the MCS-ESF, we will be able to study these rare families in a manner that will facilitate data and future genetic material sharing, testing for reproducibility across sampling frames, and an intellectual effort that will far exceed what any one isolated study could achieve on its own.