Aging in heterozygous Dnmt1-deficient mice: Effects on survival, the DNA methylation genes, and the development of amyloidosis

We previously reported that heterozygous DNA methyltransferase 1-deficient (Dnmt 1(+/-)) mice maintain T-cell immune function and DNA methylation levels with aging. whereas controls develop autoimmunity, immune senescence, and DNA hypomethylation. We therefore compared survival, cause of death, and T-cell DNA methylation gene expression during aging ill Dnmt 1(+/-) mice and controls. No difference in longevity was observed, but greater numbers of Dnmt 1(+/-) mice developed jejunal apolipoprotein All amyloidosis. Both groups showed decreased Dnmt 1 expression with aging. However, expression of the de novo methyltransferases Dnmt3a and Dnmt3b increased with aging in stimulated T cells from control mice. MeCP2, a methylcytosine binding protein that participates in maintenance DNA methylation, increased with age in Dnmt 1(+/-) mice, suggesting a mechanism for the sustained DNA methylation levels. This model thus provides potential mechanisms for DNA methylation changes of aging, and suggests that changes in DNA methylation may contribute to some forms of amyloidosis that develop with aging.