Nitric oxide activates telomerase and delays endothelial cell senescence

Endothelial cells (ECs) undergo a limited number of cell divisions, ultimat ely stop dividing, and enter a state that is designated replicative senesce nce. Shortening of telomeres is believed to be a molecular clock that trigg ers senescence. Telomerase, a RNA-directed DNA polymerase, extends telomere s of eukaryotic chromosomes and delays the development of senescence. in th is study, we examined telomere length and the activity of telomerase during aging of human ECs in culture and elucidated the effect of nitric oxide (N O). A significant increase in senescent cells as detected by acidic beta-ga lactosidase expression and a reduction of telomere length were found after 11 passages. Telomerase activity was reduced after the seventh passage, the reby preceding the development of EC senescence. The repeated addition of t he NO donor S-nitroso-penicillamine significantly reduced EC senescence and delayed age-dependent inhibition of telomerase activity, whereas inhibitio n of endogenous NO synthesis had an adverse effect. Taken together, our res ults demonstrate that telomerase inactivation precedes EC aging, NO prevent s age-related downregulation of telomerase activity and delays EC senescenc e.