DNA methylation dynamics in aging: how far are we from understanding the mechanisms?

DNA methylation is currently the most promising molecular marker for monitoring aging and predicting life expectancy. However, the mechanisms underlying age-related DNA methylation changes remain mostly undiscovered. Here we discuss the current knowledge of the dynamic nature of DNA epigenome landscape in mammals, and propose putative molecular mechanisms for aging-associated DNA epigenetic changes. Specifically, we describe age-related variations of methylcytosine and its oxidative derivatives in relation to the dynamics of chromatin structure, histone post-translational modifications and their modulators. Finally, we are proposing a conceptual framework that could explain the complex nature of the effects of age on DNA methylation patterns. This combines the accumulation of DNA methylation noise and also all of the predictable, site-specific DNA methylation changes. Gathering information in this area would pave the way for future investigation aimed at establishing a possible causative role of epigenetic mechanisms in aging.