Aspirin reduces endothelial cell senescence

• Published in: Biochemical and biophysical research communications Vol. 334; no. 4; pp. 1226 - 1232
• Main Authors: Bode-Böger, Stefanie M., Martens-Lobenhoffer, Jens, Täger, Michael, Schröder, Henning, Scalera, Fortunato
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.09.2005
• Subjects: Aging; Aspirin; Aspirin - administration & dosage; Asymmetric dimethylarginine; Cells, Cultured; Cellular Senescence - drug effects; Cellular Senescence - physiology; Cyclic GMP - metabolism; Dimethylarginine dimethylaminohydrolase; Dose-Response Relationship, Drug; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Humans; l-NAME; Nitric oxide; Nitric Oxide - metabolism; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Senescence; Telomerase; Oxidative stress; Aspirin; Reactive oxygen species; Senescence; Dimethylarginine dimethylaminohydrolase; l-NAME; Nitric oxide; Aging; Asymmetric dimethylarginine; Telomerase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.07.014

We report here the effect of aspirin on the onset of replicative senescence. Endothelial cells that were cultured until cumulative population doublings 40 showed clear signs of aging. Incubation with aspirin inhibited senescence-associated β-galactosidase activity and increased telomerase activity. Along with the delayed onset of senescence, aspirin decreased reactive oxygen species and increased nitric oxide (NO) and cGMP levels. Furthermore, aspirin reduced the elaboration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, and up-regulated the activity of dimethylarginine dimethylaminohydrolase, the enzyme that degrades ADMA. These effects were specific in that other nonsteroidal anti-inflammatory drugs, such as ibuprofen or acetaminophen, did not prevent the onset of endothelial senescence. The NO synthase inhibitor l-NAME, but not its inactive d-enantiomer, led to complete inhibition of aspirin-delayed senescence. These findings demonstrate that aspirin delays the onset of endothelial senescence by preventing a decrease in NO formation/generation. This might provide a therapeutic strategy aimed at blocking aging-induced NO inhibition.