Abstract Atherosclerosis is an inflammatory disease promoted by oxidized low density lipoprotein (LDL). High density lipoprotein (HDL) is an important antioxidant, protecting LDL and itself from oxidation and by detoxifying the hydroperoxides from oxidized LDL. Paraoxonase, encoded by the PON1 gene, is an enzyme involved in oxidant defense by hydrolyzing oxidized lipids, including oxLDL, and in detoxification of organophosphate pesticides. Aging is the major risk factor for developing atherosclerosis and as paraoxonase is responsible for the antioxidant effect of HDL, aging might be accompanied by alterations in paraoxonase activity and/or expression. Here we report the analysis of porcine PON1 mRNA expression and PON1 promoter methylation status during pig aging. PON1 mRNA expression was detected exclusively in liver and kidney using RNAseq analysis. An increase in PON1 transcript level was observed in porcine liver during aging. In contrast, no change in PON1 mRNA expression was found in kidney. The DNA methylation status was examined in a discrete region of the PON1 promoter and no significant changes were observed in liver during pig aging. However, a high methylation level was observed in occipital cortex correlating with no PON1 expression. Therefore, methylation might be one determinant of PON1 expression.