Tissue-specific modification of clock methylation in aging mice.

BACKGROUND: Circadian rhythms tend to change as animals age; however, the molecular mechanisms underlying these are not yet fully understood. OBJECTIVE: To investigate whether the DNA methylation of clock genes changes with age and contributes to circadian dysfunction in aged animals. METHODS: We examined the methylation of clock promoters in the stomach, kidney, striatum, and spleen by using a methylation-specific polymerase chain reaction (MSP) assay. RESULTS: Our results show that different tissues exhibit specific patterns of clock methylation. Additionally, methylation frequency decreased significantly in older mice at the Per1 promoter in the stomach, but it was significantly increased in older mice at the Cry1, Bmal2, and Npas2 promoters in the spleen. CONCLUSION: The findings from our study suggest that DNA methylation contribute to agerelated changes in circadian rhythms in certain slave oscillators.