Age-Related Changes in DNA Methylation Associated with Shifting Th1/Th2 Balance

This study was conducted in order to explore age-related changes in the production of Th1 and Th2 cytokines and determine the corresponding status of DNA methylation. The plasma IL-4 and IFN-γ levels and expression of Th-related cytokines and transcription factors in CD4+ splenocytes were observed in mice at different weeks of age. The DNA methylation levels of IL-4 and IFN-γ promoters and the related regulatory regions in CD4+ splenocytes of mice at different weeks of age were analyzed. The DNA methyltransferase (DNMT) levels in CD4+ splenocytes of mice were analyzed. Changes in plasma IL-4 and IFN-γ levels after 5-AZA injection were evaluated. Plasma IL-4 and IL-4 expression in CD4+ splenocytes declined with increasing age, while the IFN-γ expression levels increased. Th-related transcription factors showed no differences in mice at different weeks of age. The DNMT1 and DNMT3b mRNA expression did not show significant changes in CD4+ splenocytes, whereas the DNMT3a mRNA expression increased with age. DNA methylation in the IL-4 promoter was increased, while DNA methylation in the IFN-γ promoter was decreased. The methylation of RSH7, CNS-1, and HSV increased significantly with age. Age-related changes in DNA methylation may be associated with the shift in Th1/Th2 balance.