Telomerase activity and apoptosis genes as parameters of lymphocyte aging in Down syndrome patients

Abstract

It is hypothesized that Down syndrome (DS) patients are associated with abnormalities of the immune system. Accordingly, this study was conducted to measure replicative aging and apoptosis in lymphocytes, which play an important role in the immune system, before and after being biostimulated with He:Ne laser. Replicative aging was measured in terms of telomerase activity, and ETS-2 gene relative expression. Apoptosis was measured in terms of DNA fragmentation and apoptosis genes (Fas, FasL and Bax) and antiapoptotic Bcl-2 protein. Results showed that Telomerase activity, ETS-2 mRNA expression, plasma DNA fragmentation, Fas and FasL were significantly higher among DS patients compared to controls: Telomerase activity (1.5±0.5 vs. 0.9±0.4, p<0.001); ETS2 mRNA expression (0.6±0.1 vs. 0.43±0.04, p<0.0001); plasma DNA fragmentation (0.45%±0.12 vs. 0.2%±0.1, p<0.0001); Fas protein (5.3±1.2 vs. 2.3±0.2, p<0.0001); FasL mRNA relative expression (0.37±0.05 vs. 0.24±0.01, p<0.001); Bax mRNA relative expression (0.9±0.1 vs. 0.5±0.1, p<0.00001). Bcl-2 protein was significantly low in DS patients compared to controls (8.6±1.3 vs. 10±2.1, p<0.01). He:Ne laser biostimulation applied to evaluate lymphocytes’ response significantly increased the former parameters in DS patients compared to their level before irradiation, except for Bcl-2, which was significantly decreased. In conclusion: increased telomerase activity associated with increased activity and overexpression of ETS-2 on chromosome 21 in DS patients may contribute to the increased rate of early senescence in circulating lymphocytes, which consequently contributes to the abnormalities of the immune system observed in DS. Increased apoptosis is due to increased oxidative stress, which induces an increase in the apoptotic genes Bax, Fas and FasL accompanied by a decrease in the antiapoptotic gene Bcl-2.