The Utah Study of Fertility, Longevity and Aging

犹他州生育力、寿命和衰老研究

• 批准号: 6602282
• 负责人: Ken R Smith
• 金额: $ 108.93万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-16 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6602282
• 关键词: aging; chronic disease /disorder; clinical research; environmental stressor; epidemiology; family genetics; fertility; genetic susceptibility; human data; human subject; human very old age (85+); linkage mapping; longevity; longitudinal human study; medical records

DESCRIPTION (provided by investigator): Humans vary widely in their age at death and health status over their life course. In addition, individuals appear to age at different rates. We consider the general hypothesis that a constellation of factors, both genetic and environmental in origin, affect the rate at which people age and their longevity. To test this hypothesis, we propose to measure biodemographic features of aging: exceptional longevity, slow reproductive senescence and their co-aggregation in extended families. Our data are obtained from a vast store of information on pedigrees from a large defined population. These data will help to identify families of interest on whom to measure epidemiologic, social, cognitive, physiological and molecular traits believed to be related to aging and longevity. We will examine associations among these characteristics in these families to better define an aging phenotype associated with exceptional longevity. We will genotype exceptionally long-lived individuals from these families, their offspring, and their nieces/nephews in an attempt to discover genes associated with a delayed aging phenotype. We adopt an interdisciplinary approach and use a large population setting to better understand the genetic and environmental bases for phenotypic variation in aging leading to exceptional longevity. We have four specific aims: (1) to combine excess longevity and reproductive senescence to model a familial Delayed Aging Phenotype; (2) to test the association between the familial Delayed Aging Phenotype and resistance to age-related chronic diseases and environmental stressors; (3) to conduct genetic linkage studies to identify linked markers and haplotypes associated with exceptional longevity; and (4) to assess whether offspring of long-lived parents have favorable measures of phenotypic traits that suggest an intermediate phenotype for slow aging. We will use the Utah Population Database that contains medical and demographic records on six million individuals merged into multi-generational families. Aims associated with morbidity outcomes will be based on existing Utah Cancer Registry records and new links to Medicare records. This study will help to determine whether there are genetic variants associated with familial longevity and how such genes affect the risk of important traits and diseases associated with aging.

描述(由研究人员提供)：人类死亡时的年龄和生命过程中的健康状况差异很大。此外，每个人的衰老速度似乎也不同。我们考虑一种普遍的假设，即起源于遗传和环境的一系列因素影响着人们的衰老速度和寿命。为了验证这一假设，我们建议测量老龄化的生物统计学特征：异常长寿、缓慢的生殖衰老以及它们在大家庭中的共同聚集。我们的数据是从庞大的血统信息中获得的，这些信息来自一个庞大的确定的人口群体。这些数据将有助于确定感兴趣的家庭，以测量被认为与衰老和长寿有关的流行病学、社会、认知、生理和分子特征。我们将检查这些家系中这些特征之间的关联，以更好地定义与异常长寿相关的衰老表型。我们将对这些家庭中特别长寿的个体、他们的后代以及他们的侄女/侄子进行基因分型，试图发现与延缓衰老表型相关的基因。我们采用跨学科的方法，并使用大量的人口背景，以更好地了解导致异常长寿的衰老表型变异的遗传和环境基础。我们有四个具体的目标：(1)结合过度长寿和生殖衰老来模拟家族性延缓衰老表型；(2)测试家族性延缓衰老表型与对与年龄相关的慢性病和环境应激源的抵抗力之间的关系；(3)进行遗传连锁研究，以确定与异常长寿相关的连锁标记和单倍型；以及(4)评估长寿父母的后代是否具有有利的表型特征，表明缓慢衰老的中间表型。我们将使用犹他州人口数据库，该数据库包含合并成多代家庭的600万人的医疗和人口记录。与发病率结果相关的目标将基于犹他州癌症登记中心的现有记录和与医疗保险记录的新链接。这项研究将有助于确定是否存在与家族长寿相关的遗传变异，以及这些基因如何影响与衰老相关的重要特征和疾病的风险。