LONGEVITY IN THE AMISH

阿米什人的长寿

• 批准号: 7378820
• 负责人: WENDY S POST
• 金额: $ 1.36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378820
• 关键词: LONGEVITY; AMISH

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Longevity is a complex trait that is influenced by the interaction of the environment with multiple genes. The heritable phenotype that predicts longevity is largely undefined. Individuals who harbor longevity assurance genes may be "protected" from vascular disease. We propose identifying aging related vascular phenotypes that are associated with longevity, as part of an ongoing study of longevity in the Old Order Amish. The parent study will recruit Amish probands who lived past the age of 95 years and their offspring. The spouses of the offspring will serve as controls. Identification of a longevity phenotype will later be used to identify genes associated with protection against aging related disease. The Old Order Amish is a founder population that is relatively homogeneous, genetically and environmentally; therefore, this population is desirable for identifying phenotypic and genetic predictors of longevity. The specific aims of this study are to 1) perform electron-beam CT scanning to measure coronary calcification as a measure of subclinical atherosclerosis in 200 subjects included in an ongoing NIH funded study of longevity in the Amish. Subjects will include 100 offspring of probands who lived past the age of 95 years, and 100 spouses of these offspring; 2) to determine if offspring of long-lived probands (cases) will have less atherosclerotic plaque burden, as measured by electron beam CT coronary artery calcium scanning, than their spouses (normal controls); 3) to determine if longevity assurance genes that protect against vascular aging can be identified through association studies of single nucleotide polymorphisms (SNP) with coronary calcification. This third specific aim will be the topic of future studies whithin this cohort. Potential candidate genes include Apo E, Werner locus, and Klotho. Characterization of a longevity phenotype and later identification of genes associated with longevity may provide important mechanistic information about successful vascular aging that may help to identify future therapeutic intervention to prevent disease.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。长寿是一个复杂的特征，受到环境与多个基因相互作用的影响。预测长寿的遗传表型在很大程度上是不确定的。拥有长寿保证基因的人可能会受到“保护”，免受血管疾病的影响。我们建议识别与长寿相关的衰老相关血管表型，作为正在进行的旧秩序阿米什人长寿研究的一部分。家长研究将招募 95 岁以上的阿米什先证者及其后代。后代的配偶将作为对照。长寿表型的鉴定随后将用于鉴定与预防衰老相关疾病相关的基因。旧秩序阿米什人是一个始祖群体，在基因和环境上都相对同质。因此，这个群体对于识别长寿的表型和遗传预测因子是理想的。本研究的具体目的是 1) 对 200 名受试者进行电子束 CT 扫描来测量冠状动脉钙化，作为亚临床动脉粥样硬化的衡量标准，该研究包括 NIH 资助的一项正在进行的阿米什人长寿研究。受试者将包括 100 名活过 95 岁的先证者的后代，以及这些后代的 100 名配偶； 2) 通过电子束CT冠状动脉钙扫描测量，确定长寿先证者（病例）的后代是否比其配偶（正常对照）具有更少的动脉粥样硬化斑块负荷； 3）确定是否可以通过单核苷酸多态性（SNP）与冠状动脉钙化的关联研究来鉴定预防血管老化的长寿保证基因。第三个具体目标将是该队列未来研究的主题。潜在的候选基因包括 Apo E、Werner 基因座和 Klotho。长寿表型的表征以及随后与长寿相关的基因的鉴定可能提供有关成功血管老化的重要机制信息，这可能有助于确定未来的治疗干预以预防疾病。