Abstract 18220: High-intensity Interval Training Reduces P53 Expression and Increases Telomerase Activity in Circulating Mononuclear Cells of Untrained Subjects

Abstract

Aim: In athletes, vigorous long-term endurance training is associated with increased telomerase activity and prevention of age-dependent telomere erosion and p53 up-regulation in circulating mononuclear cells. We examined whether high-intensity interval running exercise activates cellular anti-senescent pathways in untrained healthy subjects. Methods and Results: N=10 untrained healthy subjects with normal aerobic exercise capacity (age 44±3 years, BMI 24±3kg/m2, VO2max 38±7ml/min*kg) were subjected to a supervised high-intensity interval running exercise for 3 months. Before the first and after the last training, ECG and treadmill stress tests were performed to measure training status and maximal heart rate (maxHR). The training intervention consisted of three HR-controlled training sessions per week. After warm-up four intervals consisting of 4 minutes fast running at 80-90% maxHR interspersed by 3 minutes slow running at 65-75% maxHR were performed before cool-down. Peripheral blood mononuclear cells (MNC) were isolated by density gradient centrifugation before and after training. After three months training, MNC telomerase activity was increased (145±7%; p=0.04, TRAP assay). Protein expression of the senescence marker and apoptosis regulator p53 was reduced (68±23% vs. inclusion, p<0.01). The molecular effects of interval training on MNC were associated with improvements of exercise capacity. Maximal running speed on the treadmill increased from 10.6±1.5km/h to 11.8±2.2km/h, p=0.03; physical working capacity at 150 beats/min increased from 6.6±1.4km/h to 7.4±1.6km/h, p=0.02.

Conclusion: This pilot study suggests that a high-intensity interval training over three months leads to an increase in telomerase activity and a reduction in the expression of senescence markers in circulating blood cells in healthy subjects without prior training experience. In concert with previous studies, the findings set the stage to address the question which training modality, intensity and duration are optimal to exert vascular "anti-aging effects" and whether monocyte senescence proteins are useful markers to assess the preventive potential of a training intervention.