Abstract
Background and Purpose: Advanced glycation endproducts (AGEs) produced by glycative stress are implicated in the risk of various age-related diseases. We hypothesized that DNA methylation is involved as a mechanism linking the two. This study analyzed the relationship between DNA methylation in skin samples and physical information, especially in terms of glycation stress.
Methods: Male and female Caucasian patients aged 40 - 75 years at Riga Stradins University were included (296 patients), consisting of two groups: 149 patients in the metabolic syndrome (MS) group and 147 in the non-MS group. Methylation age (MethylAge) was calculated by measuring hydroxymethylated DNA by LC-MS and matching with cohort data from the Reunis Institute. Glycative stress indices were measured by skin AGE fluorescence (SAF) with an AGE Reader (DiagnOptics, The Netherland). In addition, physical measurements and blood sex chemistry tests were performed.
Results: Items that showed significant correlations with MethylAge were chronological age (r = 0.594), waist circumference (r = 0.261), triglyceride (r = 0.317), and skin aging index (SAI, r = 0.318, p < 0.05 for each). The correlation between methylation age (y) and SAF (x) was particularly high (y = 131.9x2 - 490.1x + 491.5, R2 = 0.989, p < 0.001). The items that showed significant differences in MethylAge depending on the presence or absence of disease/lesions were MS, SAI, Sebhoroic keratosis and Lentigo type of hyperpigmentation (p < 0.05 for each). The glycation stress index SAF showed a significant correlation with the presence or absence of MS, oxidative stress index (glutathione, superoxide dismutase), and glycolipid metabolism index (fasting plasma glucose, total cholesterol, high-density lipoprotein-cholesterol).
Conclusion: Assessment of MethylAge may be an important indicator for physiological aging affected by glycative and oxidative stress. The mechanism by which these stress affects methylation age requires further investigation.
