Epigenetic regulation is critically important in mammalian development. Changes in epigenetic regulation have also been shown to play a role in the etiology of human disease, for example, hypermethylation of tumor suppressor genes in cancer. Epigenetic changes in aging, which have been studied much less frequently, are a concern because once established epigenetic profiles are only partially stable and can vary substantially as compared with the more static DNA sequence code.
The dynamics of methylation patterns in brain and liver are studied, since it is conceivable that aging cells change the expression of many of their genes in response to stress and other pro-aging physiological changes.
Imprinted genes, a subset of mammalian genes which is monoallelically expressed in a parent-of-origin manner due to epigenetic mechanisms that confer a parent-specific memory to individual cells, are our first focus of study. Hence, imprinted genes are possibly more likely to be susceptible to age-related changes than other types of epigenetic regulation.
We will present data on DNA methylation patterns of a variety of organ-specific, imprinted and not imprinted genes in brain from old and young C57BL/6 mice and in liver from a mouse model (KU80 KO) harboring a genetic defect in DNA double-strand break repair, showing multiple symptoms of premature aging.