Résumé
Ambient air particulate matter (PM) induces senescence in human skin cells. However, the underlying mechanismsremain largely unknown. We investigated how epigenetic regulatory mechanisms participate in cellular senescenceinduced by PM with a diameter <2.5 (PM 2.5) in human keratinocytes and mouse skin tissues. PM2.5 -treated cellsexhibited characteristics of cellular senescence. PM 2.5 induced a decrease in DNA methyltransferase (DNMT) expressionand an increase in DNA demethylase (ten–eleven translocation; TET) expression, leading to hypomethylation of thep16 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 PM2.5 -treated keratinocytes, whereas TET1 andMLL1 binding increased, leading to decreased histone H3 lysine 27 trimethylation (H3K27Me3) and increasedH3K4Me3 in the promoter of p16 INK4A. PM2.5 -induced senescence involved aryl hydrocarbon receptor (AhR)-inducedreactive oxygen species (ROS) production. ROS scavenging dampened PM2.5 -induced cellular senescence throughregulation of DNA and histone methylation. Altogether, our work shows that skin senescence induced byenvironmental PM 2.5 occurs through ROS-dependent the epigenetic modification of senescence-associated geneexpression. Our findings provide information for the design of preventive and therapeutic strategies against skinsenescence, particularly in light of the increasing problem of PM 2.5 exposure due to air pollution.