Abstract
Aging is the main risk factor for most chronic diseases. Epigenetic mechanisms, such as DNA methylation (DNAm) plays a pivotal role in the regulation of physiological responses that can vary along lifespan. The aim of this research was to analyze the association between leukocyte DNAm in genes involved in longevity and the occurrence of obesity and related metabolic alterations in an adult population. Subjects from the MENA cohort (n=474) were categorized according to age (<45 vs 45>) and the presence of metabolic alterations: increased waist circumference, hypercholesterolemia, insulin resistance, and metabolic syndrome. The methylation levels of 58 CpG sites located at genes involved in longevity-regulating pathways were strongly correlated (FDR-adjusted< 0.0001) with BMI. Fifteen of them were differentially methylated (p<0.05) between younger and older subjects that exhibited at least one metabolic alteration. Six of these CpG sites, located at MTOR (cg08862778), ULK1 (cg07199894), ADCY6 (cg11658986), IGF1R (cg01284192), CREB5 (cg11301281), and RELA (cg08128650), were common to the metabolic traits, and CREB5, RELA, and ULK1 were statistically associated with age. In summary, leukocyte DNAm levels of several CpG sites located at genes involved in longevity-regulating pathways were associated with obesity and metabolic syndrome traits, suggesting a role of DNAm in aging-related metabolic alterations.
Highlights
Improvements in health care and nutrition, more efficient infrastructure and access to basic supplies have been increasing life expectancy worldwide, leading to a shift towards older populations (Methods for Life Expectancy and Healthy Life Expectancy, WHO (2014))
Population was divided according to median age (45 years) and as expected, older subjects (≥ 45 years) presented increased body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressure (HT), insulin resistance (IR), and circulating cholesterol and triglyceride levels when compared to younger individuals
Among the 13,268 cytosinephosphate-guanine site (CpG) significantly associated with BMI (p
Summary
Improvements in health care and nutrition, more efficient infrastructure and access to basic supplies have been increasing life expectancy worldwide, leading to a shift towards older populations (Methods for Life Expectancy and Healthy Life Expectancy, WHO (2014)). This extended lifespan is associated with an increase in the prevalence of age-related diseases [1]. A recent report has associated www.aging‐us.com obesity with shorter longevity [2]; where normal-weight men lived on average about six years more than morbidly obese men, whereas morbidly obese women tended to live two years less than normal-weight women. It has been estimated that obesity-related diseases increase lessened life years by 0.2 to 11.7 years depending on age BMI, gender and ethnic background [3]
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