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 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 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.