Epigenetic drift versus the Epigenetic clock: distinct relationships between DNA methylation and aging
Commentary written by Meaghan Jones and Sarah Goodman
Your genome is defined at conception, and aside from rare mutations, it is relatively fixed over your lifetime. Your epigenome, on the other hand, is a balance of responsiveness and heritability. The epigenome can change with specific exposures or experiences, and has also been shown to change with age. Currently, one central question to epigenetics and age is whether the changes observed are simply a result of the accumulation of exposures and experiences, or whether there is an underlying program. In our recent review, we sought to distinguish between aging-related epigenetic changes and the age-associated epigenetic embedding of exposures using the concepts of the epigenetic clock and epigenetic drift, respectively. While these terms already existed in the literature, we have attempted to define them and discuss how their similarities and differences might together help to shape the epigenetic landscape over a lifetime.
Epigenetic drift was identified many years ago, first in cell culture and then in human twins. Twins begin their lives very similar epigenetically, but become more and more distinct with age as their experiences and exposures begin to differ immediately after birth. We define epigenetic drift as a collection of epigenetic changes acquired with age, which could be associated with the environment in which a person ages. Sites of epigenetic drift are unique to an individual and therefore contribute to increasing discordance between human epigenomes over time.
The epigenetic clock, on the other hand, represents a very different biological occurrence. The idea came to prominence in 2013, when Dr. Steve Horvath and others published papers identifying sites of DNA methylation in the genome that were so reliably associated with age that they could be used to predict biological age. Though the specific sites differed across studies, these publications led to our idea that the epigenetic clock broadly reflects the process of aging. It occurs in addition to the increasing variability caused by epigenetic drift, at sites in the genome that reliably “tick” with age. We hypothesize that while some clock sites may be common across tissues, each tissue may in fact have its own set of “ideal” clock sites.
It will be very interesting to watch the field as it unfolds and see how these two phenomena develop in the literature and contribute to new discoveries in aging research. In particular, recent work has suggested that accelerated epigenetic age is related to decreased overall or disease-specific health and increased mortality. The epigenetics of aging is a promising lead towards tracking or improving the health of an aging population.
Jones MJ, Goodman SJ, & Kobor MS (2015). DNA methylation and healthy human aging. Aging cell PMID: 25913071