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a Departments of Internal Medicine, University of Michigan, Ann Arbor
b Departments of Cell and Molecular Biology, University of Michigan, Ann Arbor
c Departments of Pathology, University of Michigan, Ann Arbor
d Departments of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor
e Ann Arbor Veterans Affairs Hospital, Michigan
Bruce Richardson, 5310 Cancer Center and Geriatrics Center Bldg., Ann Arbor, MI 48109-0940 E-mail: Brichard{at}umich.edu.
Decision Editor: Edward Masoro, PhD
DNA methylation modifies gene expression. Methylation patterns are established during ontogeny, but they change with aging, usually with a net decrease in methylation. The significance of this change in T cells is unknown, but it could contribute to autoimmunity, senescence, or both. We examined the effects of a null mutation in DNA methyltransferase 1 (Dnmt1), a gene maintaining DNA methylation patterns, on immune aging. Whereas aged control mice developed hypomethylated DNA, autoimmunity, and signs of immune senescence as predicted, the knockout mice surprisingly increased DNA methylation and developed signs of autoimmunity and senescence more slowly. To identify potential mechanisms, we compared transcripts of DNA methyltransferase and methylcytosine binding protein family members in control and knockout mice. MeCP2, a methylcytosine binding protein involved in gene suppression and chromatin inactivation, was the only transcript differentially expressed between old knockout mice and controls, and thus it is a candidate for a gene product mediating these effects.
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