title: Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall.
abstract: 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.
  
  
  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.
authors: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
authors: Christian
authors: C
authors: Werner
authors: Tobias
authors: T
authors: Fürster
authors: Thomas
authors: T
authors: Widmann
authors: Janine
authors: J
authors: Pöss
authors: Cristiana
authors: C
authors: Roggia
authors: Milad
authors: M
authors: Hanhoun
authors: Jürgen
authors: J
authors: Scharhag
authors: Nicole
authors: N
authors: Büchner
authors: Tim
authors: T
authors: Meyer
authors: Wilfried
authors: W
authors: Kindermann
authors: Judith
authors: J
authors: Haendeler
authors: Michael
authors: M
authors: Böhm
authors: Ulrich
authors: U
authors: Laufs
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001808:Blood Vessels / Q000166:cytology* / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D010805:Physical Conditioning, Animal / Q000379:methods; D005082:Physical Exertion / Q000502:physiology*; D012420:Running / Q000502:physiology; D016615:Telomere / Q000201:enzymology / Q000502:physiology; D055815:Young Adult