Age-associated changes in DNA methylation and mRNA level of the c-myc gene in spleen and liver of mice.

Age-associated changes in DNA structure and mRNA level were studied for the c-myc gene in spleen and liver of mice at 2, 14 and 26 months of age. Neither amplification nor rearrangement of the gene was detected in either tissue at any age. However, a significant alteration was observed in the methylation profile. The profile of the gene and its vicinity was determined using various methylation-sensitive restriction enzymes. In both tissues, the gene had an unmethylated domain ranging from -2 kb upstream of the 5' end of the first exon to the 3' end of the first intron. It was flanked by partially methylated regions, where age-dependent changes as well as tissue specificity were observed. In the spleen, age-related hypomethylation was observed at both the 3' and 5' sides of the domain. In contrast, hypermethylation was found in the liver only at the 3' side. The steady-state level of c-myc mRNA showed a drastic decrease in liver from youth to middle age, while splenic mRNA changed little. The correlation between the changes of mRNA and DNA methylation is discussed.