Human Telomere Genetics

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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.