Abstract 18815: Genetic Deletion of Telomerase Promotes Premature Cardiac Aging

Telomere length shortens with age and predicts the onset of cellular senescence and organ aging with progressive deterioration of function. It remains, however, to be documented whether loss of telomeric DNA in cardiac stem cells (CSCs) and myocytes is causally involved in the manifestations of the aging cardiomyopathy. To test this possibility, the third generation of mice carrying a deletion of the RNA component of telomerase (Terc-/- mice) was studied early in life at 3-12 months of age. Wild type (WT) senescent mice at 30 months of age were included in the analysis to establish whether accelerated aging in Terc-/- mice recapitulates physiological aging. Initial studies indicated that Terc-/- mice, at 4 months of age, displayed attenuated left ventricular (LV) function with respect to age-matched WT by echocardiography and hemodynamics. In contrast, severe alterations in cardiac performance were apparent at 12 months. Telomere length in Terc-/- mouse CSCs and myocytes was ~50-70% shorter than in age-ma...