Abstract 3787: Effects of Running Exercise on Aortic Telomere Regulating Proteins, Survival Pathways and Apoptosis
Background: The vasoprotective effects of physical exercise are only partially understood on the molecular level. Telomere-associated proteins affect cellular senescence and survival. We studied the molecular effects of physical exercise in aortic tissue of running and sedentary mice.
Methods: C57/Bl6 wildtype, endothelial nitric oxide synthase (ENOS) deficient and telomerase reverse transcriptase (TERT) deficient mice were randomized to voluntary running or no running wheel conditions (n=8 –10 per group).
Results: Physical exercise for 3 weeks upregulated aortic telomerase activity to 303 ± 32% (p<0.01) of sedentary controls, increased protein expression telomere-repeat binding factor (TRF) 2 (254 ± 35%, p<0.05) and reduced protein expression of the senescence / apoptosis regulators Chk2 (41 ± 12%), p53 (51 ± 12%) and p16 (64 ± 19%). Running increased mRNA expression of TRF1 (193 ± 50%), TRF2 (192 ± 14%) and of the repair protein Ku70 (365 ± 121%). These exercise-induced changes were absent in ENOS −/− and TERT −/− mice. Aortic telomere length as determined by quantitative fluorescence in-situ hybridization (QFISH) did not differ between 3 week and 6 months old sedentary or running mice (1914 ± 166 vs. 1762 ± 394 telomere fluorescence units, TFU), but was lower in 18 months old sedentary control mice (1142 ± 117 TFU, p<0.05). To test the physiologic relevance of these exercise-mediated anti-senescent pathways, vascular oxidative stress was induced in-vivo by intraperitoneal injection of 25mg/kg paraquat for 24 hours before quantification of endothelial apoptosis in the thoracic aorta. Compared to sedentary mice, paraquat increased apoptotic cell death to 581 ± 48 %, whereas apoptosis was significantly lower in mice preconditioned by 21 days voluntary exercise (320 ± 34%, p<0.001 vs. control and paraquat).
Conclusions: Voluntary physical activity upregulates aortic telomere regulating proteins which induces anti-senescent and anti-apoptotic effects mediated by ENOS and TERT independent of telomere length.