Particulate matter-induced senescence of skin keratinocytes involves oxidative stress-dependent epigenetic modifications

Abstract

Ambient air particulate matter (PM) induces senescence in human skin cells. However, the underlying mechanisms remain largely unknown. We investigated how epigenetic regulatory mechanisms participate in cellular senescence induced by PM with a diameter <2.5 (PM _2.5) in human keratinocytes and mouse skin tissues. PM _2.5-treated cells exhibited characteristics of cellular senescence. PM _2.5 induced a decrease in DNA methyltransferase (DNMT) expression and an increase in DNA demethylase (ten–eleven translocation; TET) expression, leading to hypomethylation of the p16 ^INK4A promoter region. In addition, PM _2.5 led to a decrease in polycomb EZH2 histone methyltransferase expression, whereas the expression of the epigenetic transcriptional activator MLL1 increased. Furthermore, binding of DNMT1, DNMT3B, and EZH2 to the promoter region of p16 ^INK4A decreased in PM _2.5-treated keratinocytes, whereas TET1 and MLL1 binding increased, leading to decreased histone H3 lysine 27 trimethylation (H3K27Me3) and increased H3K4Me3 in the promoter of p16 ^INK4A . PM _2.5-induced senescence involved aryl hydrocarbon receptor (AhR)-induced reactive oxygen species (ROS) production. ROS scavenging dampened PM _2.5-induced cellular senescence through regulation of DNA and histone methylation. Altogether, our work shows that skin senescence induced by environmental PM _2.5 occurs through ROS-dependent the epigenetic modification of senescence-associated gene expression. Our findings provide information for the design of preventive and therapeutic strategies against skin senescence, particularly in light of the increasing problem of PM _2.5 exposure due to air pollution.

Skin damage: counteracting the effects of air pollution

Fine particulate matter in polluted air damages skin cells by increasing oxidative stress and the expression of a protein that stops cell division. Jin Won Hyun and colleagues at Jeju National University School of Medicine, South Korea, show that exposure to particulate matter emitted by diesel engines causes skin cell senescence. In previous studies, they reported that particulate matter exposure led to the generation of reactive oxygen species (ROS). This study shows that ROS triggers changes in DNA and histone-modifying enzymes that remove suppressive chemical markers from the gene encoding a protein associated with senescence, p16 ^INK4. Interestingly, treatment with the antioxidant N-acetylcysteine reduced both oxidative stress and p16 ^INK4 expression. These findings could guide the development of new skin-care products that prevent damage due to air pollution.