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: 7126256
• 负责人: THOMAS T PERLS
• 金额: $ 3.72万
• 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/7126256
• 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，特殊的寿命（EL）和特定的特殊生存（ES）表型是家族性的，这表明该家族性的重要组成部分是遗传性的。曾经被认为太复杂了，这是环境，行为，遗传和随机因素的难题，EL以及可能相关的ES 表型似乎可能与许多可辨别和影响力的因素有关。 该拟议的家庭研究中心的特殊生存的抽样框架将是一个基于人群的样本，以实现EL的个体样本，定义为男性年龄> = 98岁，女性年龄> 100岁，居住在马萨诸塞州和康涅狄格州。这些LLI代表了20世纪初出生的同类人群中最古老的成员。基于我们目前每年注册700名年龄验证的受试者的能力，提供额外的资源以及我们在先前基于人群的研究的经验中，我们将在这个5年项目的3年招聘期间注册809 LLIS，806个兄弟姐妹和692个LLIS的后代。由于这是一项基于人群的研究，因此我们将能够根据特定特征估算该地区，LLIS，SIBSHIP和后代的产量以及生存。 Medicare和最低数据集（MDS）数据将由Medicare和Medicaid Services中心提供，以帮助评估已注册集合的人口普查列表和代表性的敏感性，以调查LLI的区域和全国Medicare Plistization and MDS数据，以便为了增强候选人表型和增强对注册的现场数据。我们已经观察到，百岁老人的兄弟姐妹从20岁到极端的年龄就经历了他们出生队列的一半。 EIO，Kestenbaum及其同事的工作支持以下假设：存在重要的童年事件，在实现EL的能力中起着重要作用。这项拟议的努力的一部分将致力于进一步研究这些因素。在较旧的年龄，相对生存优势可以由特定的ES表型来代表，我们将在LLIS的后代和回顾性或同时在LLIS中同时进行研究。基于家庭的分析方法将用于研究家族聚集和传播方式的EL和ES表型。通过将LLI及其家人纳入基于人群的样本，并作为MCS-ESF的组成部分进行表型和分析努力，我们将能够以一种将数据和未来的遗传材料共享的方式研究这些稀有家庭，测试，以促进跨智力框架的重复性，以及一项远远超过任何一项隔离研究的智能努力，可以将其自身隔离。