Epigenetic clocks are weighted combinations of the DNA methylation status of various locations on the genome, shown to reflect chronological or biological age. DNA methylation is an epigenetic marker involved in regulating the production of proteins from their blueprint genes, and these markers constantly shift in response to circumstances, a part of the feedback loop of cellular metabolism. Definitive references to the epigenetic clock, singular, usually mean the original clock established by Steve Horvath’s team and called DNA methylation age. A fair amount of work has gone into characterizing the behavior of this clock, particularly the association of higher measured ages with age-related disease: as a general rule, at a given chronological age, people who manifest age-related disease tend to have a DNA methylation age that is higher than their chronological age. This is thought to reflect a faster pace of aging.
The challenge here is that no-one has a good idea as to what exactly these characteristic DNA methylation changes actually reflect, which underlying processes of aging cause them. Since the most important goal of any reliable metric of aging is to use it to assess potential rejuvenation therapies,