Korean Red Ginseng Attenuates Particulate Matter-Induced Senescence of Skin Keratinocytes.

Skin is a direct target of fine particulate matter (PM 2.5 ), as it is constantly exposed. Herein, we investigate whether Korean red ginseng (KRG) can inhibit PM 2.5 -induced senescence in skin keratinocytes. PM 2.5 -treated human keratinocyte cell lines and normal human epidermal keratinocytes showed characteristics of cellular senescence, including flat and enlarged forms; however, KRG suppressed them in both cell types. Moreover, while cells exposed to PM 2.5 showed a higher level of p16 INK4A expression (a senescence inducer), KRG inhibited its expression. Epigenetically, KRG decreased the expression of the ten-eleven translocation (TET) enzyme, a DNA demethylase induced by PM 2.5 , and increased the expression of DNA methyltransferases suppressed by PM 2.5 , resulting in the decreased methylation of the p16 INK4A promoter region. Additionally, KRG decreased the expression of mixed-lineage leukemia 1 (MLL1), a histone methyltransferase, and histone acetyltransferase 1 (HAT1) induced by PM 2.5 . Contrastingly, KRG increased the expression of the enhancer of zeste homolog 2, a histone methyltransferase, and histone deacetyltransferase 1 reduced by PM 2.5 . Furthermore, KRG decreased TET1, MLL1, and HAT1 binding to the p16 INK4A promoter, corresponding with the decreased mRNA expression of p16 INK4A . These results suggest that KRG exerts protection against the PM 2.5 -induced senescence of skin keratinocytes via the epigenetic regulation of p16 INK4A .