The DNA methylome as a biomarker for epigenetic instability and human aging

Methylation of DNA is intimately involved in control of mammalian/vertebrate gene expression as part of a complex epigenetic regulatory system. We hypothesize that DNA methylation at cytosine-phosphate-guanine sites (CpGs), the "DNA methylome," evolved to increase stability of the differentiated state in somatic vertebrate cells, especially post-mitotic cells, which may have helped to increase longevity. Therefore, the DNA methylome may play a key role in human aging and be an ideal source of biomarkers aging. A new model that links the methylome to chronological age has been reported by Hannum et al.( 1 ) that accurately predicts age and rate of aging from the DNA methylation state of 71 markers in human blood samples. This model may make possible the development of new anti-aging therapeutics as well as more accurately assess the impact of anti-aging regimens, such as caloric restriction and drugs such as rapamycin. Furthermore, the model reveals information loss with increased age consistent with noise/unstable diffentiation-based models of aging. The model may eventually lead to experiments to differentiate the contributions of biomolecular damage and noise/incomplete structural replication during aging.