Background-The underlying molecular mechanisms of the vasculoprotective effects of physical exercise are incompletely understood. Telomere erosion is a central component of aging, and telomere-associated proteins regulate cellular senescence and survival. This study examines the effects of exercising on vascular telomere biology and endothelial apoptosis in mice and the effects of long-term endurance training on telomere biology in humans. Methods and Results-C57/Bl6 mice were randomized to voluntary running or no running wheel conditions for 3 weeks.Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls, increased vascular expression of telomere repeat-binding factor 2 and Ku70, and reduced the expression of vascular apoptosis regulators such as cell-cycle-checkpoint kinase 2, p16, and p53. Mice preconditioned by voluntary running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transgenic mouse studies showed that endothelial nitric oxide synthase and telomerase reverse transcriptase synergize to confer endothelial stress resistance after physical activity. To test the significance of these data in humans, telomere biology in circulating leukocytes of young and middle-aged track and field athletes was analyzed. Peripheral blood leukocytes isolated from endurance athletes showed increased telomerase activity, expression of telomere-stabilizing proteins, and downregulation of cell-cycle inhibitors compared with untrained individuals. Long-term endurance training was associated with reduced leukocyte telomere erosion compared with untrained controls. Conclusions-Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis. (Circulation. 2009;120:2438-2447.)Key Words: aging Ⅲ exercise Ⅲ nitric oxide synthase Ⅲ prevention Ⅲ telomeres P hysical training is associated with improvements in exercise capacity, blood pressure regulation, insulin sensitivity, abdominal fat reduction, lipid profile, and psychosocial, hemodynamic, and inflammatory parameters. These effects contribute to an augmentation of endothelial function, delayed atherosclerotic lesion progression, and enhanced vascular collateralization in patients with diabetes mellitus, coronary artery disease, and chronic heart failure. However, despite the wealth of evidence, our understanding of the underlying molecular mechanisms, especially with regard to cellular survival and senescence, is limited.
Clinical Perspective on p 2447Aging is a predominant and independent risk factor for the development of atherosclerotic diseases. Vascular aging is characterized by impaired endothelial function and arterial stiffening. 1 On the cellular level, telomere biology is a central regulator of the aging process. Telomeres and their regulatory proteins compose t-loop structures at both ends of eukaryotic chromosomes and protect the genome from degradation during repetitive cellul...
The IABP-SHOCK II risk score can be easily calculated in daily clinical practice and strongly correlated with mortality in patients with infarct-related CS. It may help stratify patient risk for short-term mortality and might, thus, facilitate clinical decision making. (Intraaortic Balloon Pump in Cardiogenic Shock II [IABP-SHOCK II]; NCT00491036).
Long- and short-term voluntary physical exercise up-regulates cardiac telomere-stabilizing proteins and thereby induces antisenescent and protective effects, for example, to prevent doxorubicin-induced cardiomyopathy. These beneficial cardiac effects are mediated by TERT, eNOS, and IGF-1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.