Individual DNA methylation profile is correlated with age and can be targeted to modulate healthy aging and longevity

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.