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.

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

Correlation between global DNA methylation and clinical laboratorial values.

<p>Correlation between global DNA methylation and clinical laboratorial values.</p

Correlations between global DNA methylation and nutritional profile.

<p>Daily intake of A) carbohydrate, B) Lipids, C) Vitamin B6, D) Magnesium, E) Protein, F) Folic Acid), G) Vitamin B12, H) Zinc.</p

Correlations between global DNA methylation and serum dosages of proteins, albumin and alpha2 globulin.

<p>Correlations between global DNA methylation and serum dosages of proteins, albumin and alpha2 globulin.</p

Graphic representation of the age-related global DNA hypomethylation.

<p>A) Percentage of Global DNA Methylation of leukocytes from young and elder individuals. B) Stratification of global DNA methylation according to gender in both young and older groups.</p

Characteristics of the studied population.

<p>Characteristics of the studied population.</p

Representation of correlations between global DNA methylation, mean steps/day and scored functional cognition.

<p>Representation of correlations between global DNA methylation, mean steps/day and scored functional cognition.</p