Patterns of DNA methylation, the best characterized epigenetic modification, are modulated by aging.
In humans, different studies at both site-specific and genome-wide levels have reported that modifications of
DNA methylation are associated with the chronological aging process but also with the quality of aging (or biological
aging), providing new perspectives for establishing powerful biomarkers of aging.
In this article, the role of DNA methylation in aging and longevity has been reviewed by analysing literature data
about DNA methylation variations occurring during the lifetime in response to environmental factors and genetic
background, and their association with the aging process and, in particular, with the quality of aging. Special
attention has been devoted to the relationship between nuclear DNA methylation patterns, mitochondrial DNA
epigenetic modifications, and longevity. Mitochondrial DNA has recently been reported to modulate global DNA
methylation levels of the nuclear genome during the lifetime, and, in spite of the previous belief, it has been found
to be the target of methylation modifications.
Analysis of DNA methylation profiles across lifetime shows that a remodeling of the methylome occurs with age
and/or with age-related decline. Thus, it can be an excellent biomarker of aging and of the individual decline and
frailty status. The knowledge about the mechanisms underlying these modifications is crucial since it might allow
the opportunity for targeted treatment to modulate the rate of aging and longevity.