Nitric Oxide Activates Telomerase and Delays Endothelial Cell Senescence

Endothelial cells (ECs) undergo a limited number of cell divisions, ultimately stop dividing, and enter a state that is designated replicative senescence(definition).Shortening of telomeres is believed to be a molecular clock that triggers senescence.Telomerase, a RNA-directed DNA polymerase, extends telomeres of eukaryotic chromosomes and delays the development of senescence.In this study, we examined telomere(definition) length and the activity of telomerase during aging of human ECs in culture and elucidated the effect of nitric oxide (NO).A significant increase in senescent cells as detected by acidic ␤-galactosidase expression and a reduction of telomere length were found after 11 passages.Telomerase activity was reduced after the seventh passage, thereby preceding the development of EC senescence.The repeated addition of the NO donor S-nitroso-penicillamine significantly reduced EC senescence and delayed age-dependent inhibition of telomerase activity, whereas inhibition of endogenous NO synthesis had an adverse effect.Taken together, our results demonstrate that telomerase inactivation precedes EC aging.NO prevents age-related downregulation of telomerase activity and delays EC senescence.