Aspirin reduces endothelial cell senescence.
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 beta-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.
Bode-Böger
Stefanie M
SM
Institute of Clinical Pharmacology, University Hospital, Otto-von-Guericke University, Germany. stefanie.bode-boeger@medizin.uni-magdeburg.de
Martens-Lobenhoffer
Jens
J
Täger
Michael
M
Schröder
Henning
H
Scalera
Fortunato
F
D001241:Aspirin / Q000008:administration & dosage*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006152:Cyclic GMP; D001241:Aspirin