AGE-DEPENDENT TELOMERE SHORTENING IS SLOWED DOWN BY ENRICHMENT OF INTRACELLULAR VITAMIN-C VIA SUPPRESSION OF OXIDATIVE STRESS

Telomeres in eukaryotic somatic cells are destined to the age-dependen t shortening which has not been demonstrated to correlate to direct le sion of telomeric DNA by reactive oxygen intermediates (ROI); still le ss explicable is the inhibitory effect of ROI-scavenging on telomere s hortening. Here, we succeeded in artificial slowdown of age-dependent telomere shortening to 52-62% of the untreated control, in human vascu lar endothelial cells, by addition of the oxidation-resistant type of ascorbic acid (Asc), Asc-2-O-phosphate (Asc2P), which concurrently ach ieved both extension of cellular life-span and prevention of cell size enlargement indicative of cellular senescence. The results are attrib utable to a 3.9-fold more marked enrichment of intracellular Asc (Asc( in)) by addition of Asc2P, subsequently dephosphorylated before or dur ing transmembrane influx, than by addition of Asc itself, and also att ributed to diminution of intracellular ROI to 53% of the control level by Asc2P, telomerase activity was at a trace level and underwent an a ge-dependent decline, which was significantly decelerated by Asc2P. Th us, age-dependent telomere-shortening can be decelerated by suppressio n of intracellular oxidative stress and/or by telomerase retention, bo th of which are achieved by enriched Asc(in) but not by extracellular Asc overwhelmingly more abundant than Asc(in).