Impact of aging on DNA methylation

The biochemistry of aging is complex, with biologically significant changes occurring in proteins, lipids and nucleic acids. One of these changes is in the methylation of DNA. DNA methylation is a mechanism modifying gene expression. The methylation of sequences in or near regulatory elements can suppress gene expression through effects on DNA binding proteins and chromatin structure. Both increases and decreases in methylation occur with aging, depending on the tissue and the gene. These changes can have pathologic consequences, contributing to the development of malignancies and autoimmunity with aging, and possibly to other disorders as well. Thus, while aging can impact on DNA methylation, the changes in DNA methylation can also impact on aging. This review summarizes current evidence for changes in the methylation status of specific genes with aging, their impact on diseases that develop with aging, and mechanisms that may contribute to the altered DNA methylation patterns. As this field is still developing, it is anticipated that new knowledge will continue to accumulate rapidly. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.