Chronic treatment with N-acetyl-cystein delays cellular senescence in endothelial cells isolated from a subgroup of atherosclerotic patients

Mech Ageing Dev. 2008 May;129(5):261-70. doi: 10.1016/j.mad.2008.01.004. Epub 2008 Jan 20.


Endothelial senescence may contribute to the pathogenesis of age-related vascular disorders. Furthermore, chronic exposure to risk factors for cardiovascular disease (CVD) accelerates the effects of chronological aging by generating stress-dependent damages, including oxidative stress, therefore promoting stress-induced premature senescence. Our objective was to determine whether a chronic treatment with an antioxidant (N-acetyl-cystein, NAC) could delay senescence of endothelial cells (EC) isolated and cultured from arterial segments of patients with severe coronary artery disease. If EC were considered as one population (n=26), chronic NAC treatment slightly shortened telomere attrition rate associated with senescence but did not significantly delay the onset of endothelial senescence. However, in a subgroup of NAC-treated EC (n=15) cellular senescence was significantly delayed, NAC decreased lipid peroxidation (HNE), activated the catalytic subunit of telomerase (hTERT) and inhibited telomere attrition. In contrast, in another subgroup of EC (n=11) characterized by initial short telomeres, no effect of NAC on HNE and high levels of DNA damages, the antioxidant was not beneficial on senescence, suggesting an irreversible stress-dependent damage. In conclusion, chronic exposure to NAC can delay senescence of diseased EC via hTERT activation and transient telomere stabilization, unless oxidative stress-associated cell damage has become irreversible.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / pharmacology*
  • Aged
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / enzymology
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Endothelium, Vascular / cytology
  • Female
  • Humans
  • Lipid Peroxidation / drug effects
  • Male
  • Mammary Arteries / surgery
  • Middle Aged
  • Organ Culture Techniques
  • Oxidative Stress / drug effects
  • Telomerase / metabolism


  • Antioxidants
  • Telomerase
  • Acetylcysteine