The methylation of CpG dinucleotides located in key protein binding sites within gene regulatory regions often leads to gene silencing. A mechanism of aging is proposed whereby an accumulation of methylation at gene regulatory sites contributes to cellular senescence. DNA methyltransferases (DNMTs) are enzymes that catalyze the transfer of a methyl moiety from S-adenosyl-L- methionine (SAM) to the cytosine of a CpG dinucleotide and are responsible for establishing and maintaining methylation patterns in the genome. It is important to study not only transcription of the DNMTs, but also their protein expression because studies illustrate that it is possible for the enzymes to undergo posttranslational physical changes in response to stimulation even though gene transcription remains unchanged. Here, we discuss an in vitro method to study protein expression of DNMTs in aging systems. © Humana Press Inc.