Advanced Glycation End-Products Accelerate Telomere Attrition And Increase Pro-Inflammatory Mediators In Human Wil2-Ns Cells

This study investigated the effect of dietary sugars and advanced glycation end-products (AGE) on telomere dynamics in WIL2-NS cells. Dietary sugars [glucose (Glu) and fructose (Fru); 0.1 M each] were incubated with bovine serum albumin (BSA) (10 mg/ml) at 60 +/- 1 degrees C for 6 weeks to generate AGE-BSA. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed total AGE levels as 87.74 +/- 4.46 nmol/mg and 84.94 +/- 4.28 nmol/mg respectively in Glu-BSA and FruBSA model. Cell treatment studies using WIL2-NS cells were based on either glucose, fructose (each 2.5 40 mM) or AGE-BSA (200-600 pg/ml) in a dose-dependent manner for 9 days.Telomere length (TL) was measured using qPCR. Nitric oxide (NO) production and tumour necrosis factor-alpha (TNF-alpha) levels were measured in WIL2-NS culture medium. An increasing trend forTNF-alpha and NO production was observed with higher concentration of glucose (R-2 = 0.358; P= 0.019; R-2 = 0.307; P = 0.027) and fructose (R-2 = 0.669; P = 0.001; R-2 = 0.339; P = 0.006). A decreasing trend for TL (if = 0.828; P= 0.000), and an increasing trend for NO production (R-2 = 0.352; P= 0.031) were observed with increasing Glu-BSA concentrations. Fru-BSA treatment did not show significant trend on TL (R-2 = 0.135; P= 0.352) with increasing concentration, however, a significant reduction was observed at 600 pg/ml (P < 0.01) when compared to BSA treatment. No trends for TNF-alpha levels and a decreasing trend on NO production (R-2 = 0.5201; P= 0.019) was observed with increasing Fru-BSA treatment. In conclusion, this study demonstrates a potential relationship between dietary sugars, AGEs and telomere attrition. AGEs may also exert telomere shortening through the production of pro-inflammatory metabolites, which ultimately increase the risk of diabetes complications and age-related disease throughout lifespan.