A Vegan Diet Epigenetically Modulates Inflammatory Pathways and Biological Aging: Genome-Wide DNA Methylation Analysis of a One-Month Isocaloric Vegan Versus Meat-Rich Dietary Intervention

Abstract

We explored the epigenomic effects of vegan diet (VD) versus meat-rich diet (MR) and identified mechanisms that help to explain how VD affects epigenetic gene regulation. Genome-wide DNA methylation profiles in 48 healthy individuals were investigated after a 1-month randomized isocaloric dietary intervention comparing effects of a VD versus a MR. Genome-wide DNA methylation analysis revealed changes in differentially methylated positions following dietary intervention, with the VD group showing a higher degree of gene-promoter silencing in cancer-related pathways and cell growth-associated pathways (mTOR and Hippo). Cell type deconvolution indicated an anti-inflammatory shift in the VD group, characterized by decreased neutrophils and increased CD4⁺ T-cell proportions, aligning with whole blood count data. Pathway analysis reflected changes in gene promoter methylation consistent with macronutrient changes according to the diets, in that VD silenced lipid metabolism and increased insulin pathway genes. Interestingly, the health-outcome-trained epigenetic clocks PhenoAge and GrimAge indicated a deceleration of biological aging in the VD group, while the chronologically optimized Blood&Skin clock showed an opposing acceleration. Convergent evidence from pathway analysis and health-outcome epigenetic clocks thus suggests that a 1-month VD drives epigenomic changes associated with reduced cancer risk and decelerated biological aging.

Keywords

differential DNA methylation / epigenetic DNA methylation age analysis / epigenetics / genome-wide DNA methylome / nutrition / vegan diet

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