Reduction in DNA methyltransferases and alteration of DNA methylation pattern associate with mouse skin ageing.

Understanding molecular mechanisms of skin ageing is critical for developing effective anti-ageing strategies. Recently, it has been suggested that epigenetics maybe be involved in tissue ageing and age-related diseases; however, the evidence regarding skin ageing has been very limited. We ran a pilot study in mouse skin to test whether DNA methyltransferases (Dnmts), DNA demethylases such as ten-eleven translocation enzymes (Tets) and DNA methylation of gene promoters change with age by quantitative RT-PCR and methylated DNA immunoprecipitation (MeDIP)-chip. We discovered that the expression of Dnmt3a, Dnmt3b and Tet2 declines significantly with skin ageing. The genome-wide DNA methylation analysis indicates that both hypermethylation and hypomethylation in promoters of genes are taken place. Functional category of those genes suggests that inhibition of cell proliferation and activation of immune response are important adaptations likely induced by skin ageing. These findings shed new light on epigenetic regulation of skin ageing.