Age-Related Changes in the Global DNA Methylation Profile of Leukocytes Are Linked to Nutrition but Are Not Associated with the MTHFR C677T Genotype or to Functional Capacities

Abstract

Global DNA methylation of peripheral blood leukocytes has been recently proposed as a potential biomarker for disease risk. However, the amplitude of the changes in DNA methylation associated with normal aging and the impacts of environmental changes on this variation are still unclear. In this context, we evaluated the association of global DNA methylation with nutritional habits, tobacco smoking, body mass index (BMI), clinical laboratory parameters, polymorphism C677T MTHFR, functional cognition and the daily practice of physical activity in a cancer-free older population. Leukocyte global DNA methylation from 126 older individuals was quantified using a high-throughput ELISA-based method. Global DNA hypomethylation was observed in older individuals when compared to a younger population (p = 0.0469), confirming changes in DNA methylation in the aging process. Furthermore, the methylation profile of elders was correlated with the daily ingestion of carbohydrates (p = 0.0494), lipids (p = 0.0494), vitamin B6 (p = 0.0421), magnesium (p = 0.0302), and also to the serum levels of total protein (p = 0.0004), alpha 2 globulin (p = 0.0013) and albumin (p = 0.0015). No statistically significant difference was observed when global DNA methylation were stratified according to C677T MTHFR genotypes (p = 0.7200), BMI (p = 0.1170), smoking habit (p = 0.4382), physical activity in daily life (p = 0.8492), scored cognitive function (p = 0.7229) or depression state (p = 0.8301). Our data indicate that age-related variations in the global DNA methylation profile of leukocytes might be modulated by the daily intake of carbohydrates, lipids, vitamin B6, and magnesium and be associated with serum protein levels, however it is independent of C677T MTHFR genotype and not correlated with BMI, smoking habit, cognitive function or the routine physical activities.

Aberrant DNA Methylation of P16, MGMT, hMLH1 and hMSH2 Genes in Combination with the MTHFR C677T Genetic Polymorphism in Gastric Cancer

“…Hypermethylation of MGMT genes has present a significantly interaction with polymorphisms of MTHFR C677T. The relationship between DNA methylation of P16, MGMT, hMLH1 and hMLH2 genes and MTHFR polymorphisms with the cancer risk has been pointed in several studies (Chen et al, 2012;Cheng et al, 2012;de Cássia Carvalho Barbosa et al, 2012;Gomes et al, 2012). The results of our study are associated with previous results.…”

Genome-wide DNA methylation variability in adolescent monozygotic twins followed since birth

“…If the methylome is indeed dynamic throughout life, then differences in DNA methylation profiles in identical twins should increase through life. As expected, studies demonstrate that although within-pair discordances are present from birth, 36 they increase with age, [37][38][39][40][41][42][43][44][45] particularly when twins experience divergent medical histories/ environments. [46][47][48][49] In fact, Novakovic and colleagues 50 found differences during gestation, which increased with gestational age.…”

Aberrant DNA methylation of MGMT and hMLH1 genes in prediction of gastric cancer

“…Changes in the activity of folate metabolic enzymes induced by genetic polymorphisms may affect the methylation status of these genes and induce carcinogenesis (Chen et al, 2012;Gao et al, 2013 hMLH1 genes and cancer risk has been demonstrated in several studies (Chen et al, 2012;Gomes et al, 2012;Cheng et al, 2012;de Cássia Carvalho Barbosa et al, 2012). However, few studies have evaluated their association with gastric cancer risk.…”