Year Long Wheel Running Alters Telomere Dynamics and Markers of DNA Damage in Mice

Abstract

Physical activity is known to reduce the risk of morbidity and mortality from a number of chronic diseases (CVD, etc), however the molecular basis for this association remains elusive. Telomeres have been associated with many chronic diseases. PURPOSE: The purpose of this study was to investigate telomere length, telomerase enzyme activity, and markers of DNA damage and apoptosis in cardiac and skeletal muscle following 1 yr of voluntary wheel running in a mouse model. METHODS: Twenty-one 8-wk old CAST/EiJ mice were separated into individual cages with (Exercise, n=10) and without (Sedentary, n=11) access to a voluntary running wheel. Running behavior was monitored via computerized software. Telomere length and telomerase enzyme activity were determined by qRT-PCR and mRNA levels were measured by semi-quantitative PCR. RESULTS: The Exercise group averaged 6.2±2.3km running per day over the 1 yr period. Body weight did not differ between the two groups (P=0.42). Telomere length was significantly longer in the skeletal muscle of Sedentary animals (Sed=1.54±0.14 vs. Exer=1.0±0.12 AU; P=0.007). Conversely, longer telomeres were observed in cardiac muscle of the Exercise mice (Sed=0.1±0.005 vs. Exer=1.0±0.21; P=0.008). Higher telomerase activity levels were observed in skeletal muscle of Exercise mice (Exer=0.083±0.025 vs. Sed=0.018±0.005 amoles/0.43 ug protein; P=0.03), while no difference was observed for telomerase activity in cardiac muscle. Skeletal muscle mRNA levels of Exercised mice were higher for Trf1 and Pot1a, but were not different compared to Sedentary mice for Ku80, Ku70, Trf2, p53, Chk2, and Gapdh. Cardiac muscle mRNA levels of Exercise mice were higher for Trf1, Trf2, Ku80, Ku70, p16, but were not different compared to Sedentary mice for Chk2, p53, and Gapdh. CONCLUSIONS: Exercise training appears to modulate telomere length, telomerase enzyme activity, and mRNA levels of telomere binding proteins and markers of DNA damage and apoptosis in contractile tissues of mice, though in a tissue-specific manner. Support provided by NIH/NIA AG-00268 and the Dept. of Kinesiology Graduate Student Research Initiative Fund.