Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
Circulation. 2009 Dec 15;120(24):2438-47. doi: 10.1161/CIRCULATIONAHA.109.861005.
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.
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.
Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.
运动对血管的保护作用的潜在分子机制尚不完全清楚。端粒磨损是衰老的核心组成部分，端粒相关蛋白调节细胞衰老和存活。本研究探讨了运动对小鼠血管端粒生物学和内皮细胞凋亡的影响，以及长期耐力训练对人类端粒生物学的影响。
C57/Bl6 小鼠随机分为自愿跑步或无跑步轮条件 3 周。与久坐对照组相比，运动上调了胸主动脉和循环单核细胞中的端粒酶活性，增加了血管端粒重复结合因子 2 和 Ku70 的表达，并减少了血管凋亡调节因子的表达，如细胞周期检查点激酶 2、p16 和 p53。经过自愿跑步预适应的小鼠表现出脂多糖诱导的主动脉内皮细胞凋亡明显减少。转基因小鼠研究表明，内皮型一氧化氮合酶和端粒酶逆转录酶在体力活动后协同赋予内皮细胞应激抵抗能力。为了检验这些数据在人类中的意义，分析了年轻和中年田径运动员循环白细胞中的端粒生物学。与未经训练的个体相比，耐力运动员分离的外周血白细胞显示端粒酶活性增加、端粒稳定蛋白表达增加和细胞周期抑制剂下调。与未经训练的对照组相比，长期耐力训练与白细胞端粒磨损减少相关。
运动调节小鼠和人类的端粒稳定蛋白，从而防止应激诱导的血管凋亡。
