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Aspirin reduces endothelial cell senescence
Abstract
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.
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“In addition there are data suggesting that acetaminophen activates telomerase [146,147,148,149], which could lead to the immortalization of cells.”
From Cell Immortality: In Vitro Effective Techniques to Achieve and Investigate Its Applications and Challenges (2024) · cites this paper as [149]
In the citing paper
“There are other data that show that aspirin, at therapeutically relevant concentrations, prevents the senescence of endothelial cells. This effect seems to be due to increased nitric oxide (NO) synthesis and reduced oxidative stress.”
From Cell Immortality: In Vitro Effective Techniques to Achieve and Investigate Its Applications and Challenges (2024) · cites this paper as [149]
Citations
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Vascular Cell Senescence: Contribution to Atherosclerosis
Minamino, T., & Komuro, I. (2007) · Circulation Research · doi:10.1161/01.res.0000256837.40544.4a · Cited by 542
Lu, T., & Finkel, T. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.01.011 · Cited by 327
Effects of aging on angiogenesis
Lähteenvuo, J., & Rosenzweig, A. (2012) · Circulation Research · doi:10.1161/circresaha.111.246116 · Cited by 292
Vascular aging: implications for cardiovascular disease and therapy
Ghebre, Y. T., Yakubov, E., Wong, W. T., & Krishnamurthy, P. (2016) · Translational Medicine · doi:10.4172/2161-1025.1000183 · Cited by 87
Chalak, M., Hesaraki, M., Mirbahari, S. N., Yeganeh, M., Abdi, S., Rajabi, S., & Hemmatzadeh, F. (2024) · Life · doi:10.3390/life14030417 · Cited by 66
Metadata
- Authors
- Bode-Böger, S. M., Martens-Lobenhoffer, J., Täger, M., Schröder, H., & Scalera, F.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 334
- Issue
- 4
- Pages
- 1226-1232
- ISSN
- 0006-291X
- Cited by
- 85
- References
- 2
- Language
- en
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