Environmental Deflection: The Impact of Toxicant Exposures on the Aging Epigenome

Abstract

Epigenetic drift and age-related methylation have both been used in the literature to describe changes in DNA methylation that occurs with aging. However, ambiguity remains regarding the exact definition of both of these terms, and neither of these fields of study explicitly considers the impact of environmental factors on the aging epigenome. Recent twin studies have demonstrated longitudinal, pair-specific discordance in DNA methylation patterns, suggesting an effect of the environment on age-related methylation and/or epigenetic drift. Supporting this idea, other new reports have shown clear environment- and toxicant-mediated shifts away from the baseline rates of age-related methylation and epigenetic drift within an organism, a process we now term "environmental deflection." By defining and delineating environmental deflection, this contemporary review aims to highlight the effects of specific toxicological factors on the rate of DNA methylation changes that occur over the life course. In an effort to inform future epigenetics-based toxicology studies, a field of research now classified as toxicoepigenetics, we provide clear definitions and examples of "epigenetic drift" and "age-related methylation," summarize the recent evidence for environmental deflection of the aging epigenome, and discuss the potential functional effects of environmental deflection.

Epigenetics and the maintenance of developmental plasticity: extending the signalling theory framework

“…For instance, prenatal exposures to lead (Faulk et al, ) and bisphenol A (BPA) (Kochmanski et al, ) are associated with altered age‐related methylation changes. Such findings indicate that a variety of external factors may compromise signal efficacy by altering the rate of epigenetic drift (Kochmanski et al, ). However, the extent to which the environment is simply a source of external noise, rather than a force that elicits deterministic changes in the epigenome, are two separate concepts which may be difficult to disentangle empirically.…”

Age-related epigenome-wide DNA methylation and hydroxymethylation in longitudinal mouse blood

“…Predictable, unidirectional changes in DNA methylation that occur with age are referred to as 'age-related methylation.' [6,7] Separate from these predictable changes, there are also stochastic, bidirectional alterations in epigenetic variability that occur with age; these are referred to as 'epigenetic drift.' [7,8] Combined, these two processes represent 'epigenetic aging,' a phenotype of age-associated changes in the epigenome.…”

“…[6,7] Separate from these predictable changes, there are also stochastic, bidirectional alterations in epigenetic variability that occur with age; these are referred to as 'epigenetic drift.' [7,8] Combined, these two processes represent 'epigenetic aging,' a phenotype of age-associated changes in the epigenome. These age-related changes in DNA methylation have important implications for transcriptional control and protein expression, and may underlie later-life disease development.…”

Epigenetic underpinnings of developmental immunotoxicity and autoimmune disease

“…Another DNA methylation mechanism identified as an emerging concept in toxicology is epigenetic drift (i.e., drift) [12]. Drift is the divergence of the epigenome as a function of age due to stochastic changes in methylation.…”

“…Thus certain risk factors may synergistically act on an already sensitive developing immune system by modifying the methylome and downstream gene expression leading to enhanced susceptibility to autoimmunity. There are only a few studies with toxicants outlined in this review that addressed diet/obesity co-exposures [(e.g., BPA [12] and TCE ( manuscript in preparation )]. Future studies should aim to interrogate DNA methylation and gene expression events to confirm the role of epigenetic modifications when considering both exogenous and/or endogenous risk factors in the development of autoimmune disease.…”