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Asymmetric Dimethylarginine Accelerates Cellular Senescence

  • Fotunato Scalera
  • Stefanie M. Bode-Böger
Chapter
Part of the Tumor Dormancy and Cellular Quiescence and Senescence book series (DOQU, volume 2)

Abstract

Cellular senescence, a physiological state of irreversible growth arrest, might contribute to cardiovascular diseases in the elderly. Cellular senescence can be modulated by several different endogenous and exogenous factors that contribute to delay or accelerate the process of senescence. Nitric oxide (NO), formed from L-arginine by nitric oxide synthase (NOS), has antiatherogenic properties and is one of endogenous factors leading to delayed cellular senescence. Intracellular factors that decrease NO synthesis may therefore represent important targets in the accelerated cellular senescence and consequently in the development of cardiovascular diseases. Long-term treatment of human endothelial cells with asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of NOS and regarded as a novel cardiovascular risk factor, accelerates the process of cellular senescence by inhibiting NO synthesis. Additionally, ADMA accelerates the shortening of telomere length in a dose-dependent manner and inhibits the telomerase activity. Our results suggest a new mechanism through which elevated ADMA levels observed in the elderly might accelerate endothelial senescence and consequently might promote atherogenesis.

Keywords

Arginine methylation Asymmetric dimethylarginine (ADMA) Cardiovascular diseases Cellular senescence Dimethylarginine dimethylaminohydrolase (DDAH) enzymes Human endothelial cells Metabolism Symmetrical dimethylarginine (SDMA) Telomerase reverse transcriptase (TERT) 

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Institute of Clinical PharmacologyUniversity Hospital, Otto-von-Guericke UniversityMagdeburgGermany

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