Overexpression of Catalase Targeted to Mitochondria Attenuates Murine Cardiac Aging

• DOI: 10.1161/circulationaha.108.822403
• Publication Date: 2009-05-19T01:45:28Z
• Authors: Dao-Fu Dai; Luis F. Santana; Marc Vermulst; Daniela M. Tomazela; Mary J. Emond; Michael J. MacCoss; Katherine Gollahon; George M. Martin; Lawrence A. Loeb; Warren C. Ladiges; Peter S. Rabinovitch
• Keywords: Mitochondrial ROS; Senescence

Background— Age is a major risk for cardiovascular diseases. Although mitochondrial reactive oxygen species have been proposed as one of the causes aging, their role in cardiac aging remains unclear. We previously shown that overexpression catalase targeted to mitochondria (mCAT) prolongs murine median lifespan by 17% 21%. Methods and Results— used echocardiography study function cohorts wild-type mCAT mice. Changes found mice recapitulate human aging: age-dependent increases left ventricular mass index atrial dimension, worsening myocardial performance index, decline diastolic function. Cardiac accompanied accumulation protein oxidation, increased DNA mutations deletions biogenesis, fibrosis, enlarged fiber size, decreased SERCA2 protein, activation calcineurin–nuclear factor activated T-cell pathway. All these age-related changes were significantly attenuated Analysis survival 130 demonstrated echocardiographic scores significant predictors mortality. The estimated attributable mortality 2 parameters was 55%. Conclusions— This shows mouse closely recapitulates demonstrates critical impact on survival. These findings also support potential application antioxidants species–related