Exceptional survival and longevity in New England

新英格兰地区的生存率和寿命都非常出色

• 批准号: 7126247
• 负责人: THOMAS T PERLS
• 金额: $ 5.05万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7126247
• 关键词: cardiovascular disorder epidemiology; chromosome movement; clinical research; cooperative study; coping; diagnosis; disease /disorder onset; epidemiology; family genetics; gene environment interaction; genetic models; genotype; health care service utilization; human middle age (35-64); human mortality; human old age (65+); human population study; human subject; human very old age (85+); long term survivor; longevity; mathematical model; nursing homes; patient oriented research; phenotype

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.

描述（由申请人提供）：迄今为止的研究表明，异常长寿（EL）和特定异常存活（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。 EL 和可能相关的 ES 一度被认为是一个由环境、行为、遗传和随机因素组成的复杂谜题 表型似乎可能与许多可辨别和有影响的因素有关。 拟议的家庭特殊生存研究中心的抽样框架将是基于人口的实现 EL 个体样本，EL 定义为居住在马萨诸塞州和康涅狄格州的男性年龄 >= 98 岁和女性年龄 >100 岁。这些 LLI 代表了 20 世纪初出生的群体中 1% 的最年长成员。根据我们目前每年招募 700 名经年龄验证的受试者的能力、额外资源的提供以及我们之前进行的较小规模人口研究的经验，我们将在 3 年招募期间招募 809 名 LLI、806 名兄弟姐妹和 692 名 LLI 后代本项目为期5年。由于这是一项基于人群的研究，我们将能够根据特定性状估计该地区的 LLI、同胞和后代的产量以及存活率。医疗保险和最低数据集 (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名单的敏感性和登记组的代表性，调查 LLI 之间的区域和全国医疗保险利用率和 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，从 20 岁到高龄，百岁老人的兄弟姐妹的死亡率是其出生群体的一半。 EIo、Kestenbaum 及其同事的研究支持了以下假设：一些与童年相关的重要事件在实现 EL 的能力方面发挥着重要作用。这项拟议工作的一部分将致力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，我们将在 LLI 的后代中同时研究该表型，并根据表型在 LLI 中回顾性或同时进行研究。基于家族的分析方法将用于研究家族聚集的 EL 和 ES 表型以及传播模式。通过将 LLI 及其家族成员纳入基于人群的样本，并作为 MCS-ESF 的组成部分进行表型分析和分析工作，我们将能够以有利于数据和未来遗传物质的方式研究这些稀有家族共享、跨样本框架的可重复性测试以及智力努力将远远超出任何一项单独的研究本身所能实现的目标。