Exceptional survival and longevity in New England

描述（由申请人提供）：迄今为止的研究表明，异常长寿（EL）和特定的异常生存（ES）表型是家族性的，并表明该家族性的一个重要组成部分是遗传的。EL和可能相关的ES曾经被认为是环境、行为、遗传和随机因素的复杂难题， 表型似乎可能与许多可辨别的和有影响的因素有关。 这个拟议的家庭特殊生存研究中心的抽样框架将是一个以人口为基础的样本，其中包括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代表了世纪之交出生的队列中1%最年长的成员。根据我们目前每年入组700例经年龄验证的受试者的能力、提供的额外资源以及我们之前基于较小人群的研究的经验，我们将在本5年项目的3年招募期内入组809例LLI、806例兄弟姐妹和692例LLI后代。由于这是一项基于人群的研究，我们将能够估计该地区的LLI产量，同胞和后代以及根据特定性状的存活率。医疗保险和最小数据集（MDS）数据将由医疗保险和医疗补助服务中心提供，以帮助衡量人口普查列表的敏感性和入组集的代表性，调查区域和全国范围内的医疗保险利用率和LLI中的MDS数据，以生成候选ES表型并增加入组受试者的表型数据。我们观察到，百岁老人的兄弟姐妹从20岁到极端老年的死亡率是他们出生队列的一半。EIO，Kestenbaum和同事的工作支持这一假设，即有重要的童年相关事件在实现EL的能力中发挥重要作用。这项拟议工作的一部分将专门用于进一步调查这些因素。在年龄较大时，相对生存优势可以通过特定的ES表型来表征，我们将同时在LLI的后代中进行研究，并根据表型在LLI中进行回顾性或同时研究。以家庭为基础的分析方法将被用来调查EL和ES表型的家庭聚集和传播方式。通过在基于人群的样本中招募LLI及其家庭成员，并作为MCS-ESF的一个组成部分进行表型分析和分析工作，我们将能够以一种促进数据和未来遗传物质共享的方式研究这些罕见的家庭，测试采样框架的再现性，以及远远超过任何一项孤立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.