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© 1993 Oxford University Press

Genetic Mechanisms

Biological Significance of DNA Methylation in the Ageing Process

Tetsuya Ono, Yoshihiko Uehara, Akihiro Kurishita, Riichi Tawa and Hiromu Sakurai

Department of Radiation Research Tohoku University School of Medicine Seiryo-Machi, 2-1, Aoba-ku, Sendai, 980, Japan
Department of Analytical Chemistry I, Kyoto Pharmaceutical University Misasagi, Yamashina-ku, Kyoto, 607, Japan

Present address: Institute for Liver Research, Kansai Medical University Moriguchi, Osaka, 570, Japan

In order to understand the possible importance of DNA methylation in ageing, characteristics of its age-associated changes were examined in mouse and man. The total methylated deoxycytidine level in the genome decreased in the senescent period in mouse liver, but not in mouse brain and human liver. The examination of DNA methylation in each individual gene revealed that only a few genes showed alteration in the senescent phase while many genes change in the maturation period. The alterations were gene- and tissue-specific. Comparison of short-living mouse and long-living man for the age-associated changes of the c-myc gene methylation revealed that the rate of change in mouse was about 20 times faster than that in man. This suggests a deep involvement of DNA methylation in ageing. Further investigations into the causes and consequences of the changes would clarify a basic mechanism of ageing.


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