Telomere Length as a Marker of Cardiovascular Aging

端粒长度作为心血管衰老的标志

• 批准号: 6942239
• 负责人: ELLEN W. DEMERATH
• 金额: $ 7.18万
• 依托单位: WRIGHT STATE UNIVERSITY
• 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 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6942239
• 关键词: adolescence (12-20); adult human (21+); age difference; alcoholic beverage consumption; biomarker; blood pressure; body composition; cardiovascular disorder diagnosis; cardiovascular disorder risk; cell adhesion molecules; cholesterol; clinical research; diagnosis design /evaluation; gender difference; hormone therapy; human puberty; human subject; longitudinal human study; menopause; physical fitness; polymerase chain reaction; smoking; telomere

DESCRIPTION (provided by applicant): Functional Senescence (Research Objective #18). The proposed research study will examine telomere length as a marker of cardiovascular aging in humans. Telomeres are non-coding functional repeat sequences at the ends of chromosomes [5' (TTAGGG)n -3'], a predictable amount of which is lost at each cell division. In this way, the length of telomeric DNA is a "mitotic clock" tracking the history of cell replication in a tissue. When telomeres reach a critically short length, cells become senescent, and a cascade of changes in gene expression and function are initiated. Thus, the loss of telomeric DNA may also effect declines in tissue function. Recent work suggests blood telomere length is a strong predictor of cardiovascular mortality, but the extent to which telomere length actually tracks the functional antecedants of cardiovascular death is unknown. Because telomere length is highly heritable, it may also be a powerful genetic marker of cardiovascular aging for genetic epidemiologic studies. A more thorough understanding of telomere biology during normal growth and aging is required, however, before telomere length may be effectively used in the epidemiologic context. In response to the NIA's "Pilot Research Grant Program" (R03 PAR-03-056), a feasibility study is proposed that will examine a new marker of biological aging, telomere length from blood DNA, as a proxy measure for cardiovascular senescence. Using an existing database of prospective cardiovascular disease (CVD) risk factor data from a well-defined longitudinal cohort, matched with stored DNA samples for each individual, we aim to determine how telomere length corresponds to changes in CVD risk factors. The specific aims of the proposed study are: 1) To estimate telomere length in 350 Fels Longitudinal Study participants aged 8-82 years using quantitative PCR, 2) To examine the effects of sex, age, puberty and menopause on telomere length, 3) To test the hypothesis that individuals with shorter telomeres have more deleterious changes in blood pressure and pulse pressure, blood lipid and lipoprotein concentrations, inflammatory markers, and aerobic fitness, and 4) To explore the impact that major lifestyle factors (tobacco and alcohol consumption, physical activity, and exogenous hormone use) have on telomere length. At the conclusion of this two-year study, we will have the first estimates of the relationship between telomere length and serial changes in cardiovascular health in children and adults of both sexes. Telomeric DNA length may thus be found to be a valuable plasma biomarker for the prediction and monitoring of cardiovascular health and aging.

描述（由申请人提供）：功能衰老（研究目标＃18）。 拟议的研究将研究端粒长度作为人类心血管衰老的标志。端粒是染色体末端的非编码功能重复序列[5'（ttaggg）n -3']，每个细胞分裂都丢失了可预测的量。这样，端粒DNA的长度是跟踪组织中细胞复制史的“有丝分裂时钟”。当端粒的长度较短时，细胞会变成衰老，并且启动了基因表达和功能变化的级联。因此，端粒DNA的丧失也可能影响组织功能下降。最近的工作表明，血端：长度是心血管死亡率的有力预测指标，但是端粒长度实际跟踪心血管死亡的功能前牙的程度尚不清楚。由于端粒长度是高度遗传的，因此它也可能是用于遗传流行病学研究的心血管衰老的强大遗传标记。但是，在流行病学环境中可以有效地使用端粒长度之前，需要在正常生长和衰老期间对端粒生物学有更透彻的了解。为了响应NIA的“试点研究赠款计划”（R03 PAR-03-056），提出了一项可行性研究，该研究将研究一个新的生物衰老，血液DNA的端粒长度标记，作为心血管衰老的代理。我们使用现有的纵向纵向队列中的前瞻性心血管疾病（CVD）风险因素数据数据库，并与每个人的存储DNA样品相匹配，我们旨在确定端粒长度如何与CVD风险因素的变化相对应。拟议研究的具体目的是：1） estimate telomere length in 350 Fels Longitudinal Study participants aged 8-82 years using quantitative PCR, 2) To examine the effects of sex, age, puberty and menopause on telomere length, 3) To test the hypothesis that individuals with shorter telomeres have more deleterious changes in blood pressure and pulse pressure, blood lipid and lipoprotein concentrations, inflammatory markers, and aerobic fitness, and 4) To探索主要的生活方式因素（烟草和饮酒，体育锻炼和外源性激素的使用）对端粒长度的影响。在这项为期两年的研究结束时，我们将对两性儿童和成人心血管健康的端粒长度与序列变化之间的关系进行首次估计。因此，可以发现端粒DNA长度是预测和监测心血管健康和衰老的有价值的血浆生物标志物。