Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall

Circulation. 2009 Dec 15;120(24):2438-47. doi: 10.1161/CIRCULATIONAHA.109.861005.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Blood Vessels / cytology*
  • Blood Vessels / physiology*
  • Cellular Senescence / physiology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology
  • Exercise / physiology*
  • Female
  • Humans
  • Leukocytes / cytology*
  • Leukocytes / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged
  • Physical Conditioning, Animal* / methods
  • Physical Exertion / physiology*
  • Running / physiology
  • Telomere / enzymology
  • Telomere / physiology
  • Young Adult