Table_1_Mini Nutritional Assessment Scores Indicate Higher Risk for Prospective Mortality and Contrasting Correlation With Age-Related Epigenetic Biomarkers.DOCX

The plasticity of the individual epigenetic landscape that goes to countless rearrangements throughout life is closely the reflection of environmental factors such as chemical exposure, socio-economic status and nutrient intakes both early and late in life. The Mini Nutritional Assessment (MNA) is a well-validated tool for assessing malnutrition in old people. It includes 6 (MNA-SF) or 18 (MNA-LF) self-reported questions derived from general, anthropometric, dietary, and self- assessment. We evaluated the association between the nutritional status, as measured by MNA, and methylation biomarkers we previously demonstrated to be associated with chronological and biological age in human. We found that malnutrition is positively correlated with DNA methylation status at the global level, in line with our previous reports. On the contrary, most of the sites located within specific genes, which were previously reported to be correlated with chronological and biological aging, showed to be not affected by malnutrition, or even to have correlations with malnutrition opposite to those previously reported with frailty. These results may suggest that malnutrition is among the first effects of disability and other age- related problems and a generalized non-specific epigenetic remodeling may be the initial response of the organism. By contrast, the fine remodeling of specific genomic sites is scarcely affected by malnutrition and may respond to a more complex interaction of different factors. Therefore, although malnutrition in the elderly is certainly a risk factor for survival, this is partially independent of the aging process of the organism which leads to the methylation remodeling previously described to measure chronological and biological aging.