Anti-oxidant treatment improves cardiac dysfunction in a murine model of premature ageing.

Bmal1 (brain and muscle ARNT-like protein-1) deficient (Bmal1) mice prematurely age due to an increased reactive oxygen species (ROS) production. These mice also show a decline in cardiac function with age. We investigated whether an anti-oxidant treatment can ameliorate the declining cardiac function in prematurely aged Bmal1 mice. Male Bmal1 and wild-type (Bmal1) mice were exposed for 15 weeks to a high fat and high cholesterol diet with or without the anti-oxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL; 5 mmol/l; in drinking water during the last 10 weeks). Echocardiographic analysis revealed that TEMPOL treatment of Bmal1 mice normalized cardiac function, as evidenced by a decrease in left ventricular diastolic and systolic internal diameters, and by an increase in fractional shortening and ejection fraction. The anti-oxidant did not affect cardiac function in Bmal1 mice. Although TEMPOL did not influence cardiac ROS levels in Bmal1 mice, it significantly protected Bmal1 cardiac telomeres from oxidation, as evidenced by a reduction in the telomere damage score (0.11 ± 0.012% vs. 0.16 ± 0.015%; P = 0.028). Thus, anti-oxidant treatment normalized cardiac function of Bmal1 mice, probably in part by scavenging ROS.