Changes in cytosine methylation status of several genes have been implicated in the aging process. We have examined methylation status of differentially methylated regions of insulin-like growth factor II: receptor gene during mouse senescence. Bisulfite-aided genomic sequencing revealed that methylated CpG residues were extended beyond the 3' boundary of de novo methylation sequence of DMR2 in aged mice. Furthermore, the de novo methylation of DMR2 in aged mice was associated with decreased expression of antisense transcript which recruits DMR2 as a promoter. On the contrary, methylation status of DMR1 was well-maintained during senescence. Accordingly, no significant changes in expression levels of sense transcripts were observed during the course of mouse aging.