Changes of DNA methylation in mouse brain and muscle during aging

Abstract

To evaluate the epigenetic theory of aging that proposes changes in epigenetic states of genes constitute a major cause of mammalian aging, sites of differential DNA methylation between young and aged mice were determined in genes exhibiting pronounced differences at their expression levels during aging. The status of DNA methylation and expression levels of four genes in mouse muscle and brain were investigated by bisulfite-sequencing and RT-PCR analysis, respectively. Two distinguishing patterns of DNA methylation changes were observed. A single site of DNA methylation within RhoB promoter was identified to be demethylated in the skeletal muscle of aged mice. The observed demethylation at RhoB correlates well with the previous report that the RhoB expression is increased in aged mouse muscle. A sporadic and irregular pattern of DNA methylation was observed at the GDNF promoter region among young mice. The CpG methylation patterns in the region exhibited a transition to an orderly fashion in the brain of aged mouse. The transition to a more stereotypic pattern in aged mice than in young mice contrasts our previous data with the CpGs of the Igf2r region. No changes in DNA methylation of GADD45 and CathepsinD were found during aging, while the expression levels of those genes were increased in mouse skeletal muscle and brain during aging. These results suggest that each gene exhibits its unique transition patterns of DNA methylation in the CpG island in accordance with the changes of its expression level during senescence.