Human Telomere Genetics

描述(由申请人提供)：随着端粒在细胞衰老中发挥关键作用变得明显，衰老研究已经采取了一个新的维度。最近的研究有力地表明，端粒生物学也参与了人类衰老的疾病。在人类中，端粒长度相对较短，女性端粒长度比男性长，高度可遗传，高度可变，关于复制体细胞，与捐赠者的年龄成反比。此外，调整年龄后，端粒长度与心血管老化的多个指标相关。 活性氧物种加速了端粒的磨损速度，活性氧物种是衰老和与衰老相关的疾病(包括心血管疾病)的主要决定因素。该提案的最终目标是识别决定人类端粒长度的基因。该项目的具体目标是：1.测量家庭心脏研究-冠脉钙质扫描(FHS-SCAN)个体的端粒长度，如白细胞所表达的；2.确定含有影响端粒长度的基因的遗传位点；3.在有证据表明存在连锁的区域中调查候选基因。结果将有助于将基因定义为端粒长度的决定因素。这些信息将导致新的诊断和治疗方法来治疗与年龄有关的疾病。

DESCRIPTION (provided by applicant): Aging research has undertaken a new dimension as it became evident that telomeres play a key function in cellular senescence. Recent studies strongly suggest that telomere biology is also involved in diseases of human aging. In humans, telomere length is relatively short, longer in women than men, highly heritable, highly variable, and with regard to replicating somatic cells, inversely related to donor age. In addition, after age-adjustment, telomere length is correlated with a number of indices of cardiovascular aging. Telomere attrition rate is accelerated by reactive oxygen species, which are major determinants in aging and diseases associated with aging, including cardiovascular diseases. The ultimate objective of the proposal is to identify genes that determine the length of human telomeres. The specific aims of this project are: 1. To measure telomere length, as expressed in white blood cells, in individuals from the Family Heart Study - Coronary Calcium Scan (FHS-SCAN); 2. To identify genetic loci harboring genes accounting for telomere length; 3. To investigate candidate genes in regions with evidence for linkage. Results will serve to define genes as determinants of telomere length. Such information would lead to new diagnostic and therapeutic approaches to treat age-related diseases.