WI-38 senescence is associated with global and site-specific hypomethylation.

Cellular senescence plays an important role in the age-dependent functional decline of organs and organ systems, as well as in age-related pathologies, such as cancer. Therefore, a better understanding of its underlying molecular mechanisms is crucial in the search for intervening measures. In this study, we considered the role of DNA methylation in senescence. We found that senescence is associated with global DNA hypomethylation, but also involves site-specific DNA hypo- and hypermethylation. In some cases, this differential methylation may affect gene expression and thereby modulate functional processes within cells. However, the majority of the CpG sites that were differentially methylated did not correspond with altered gene expression, suggesting that DNA methylation affects senescence by other means also, such as, for instance, genome stability.