Considerable epidemiological, experimental and clinical data have amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. This relationship reflects plastic responses made by the developing organism as an evolved strategy to cope with immediate or predicted circumstances, to maximize fitness in the context of the range of environments potentially faced. There is now increasing evidence, both in animals and humans, that such developmental plasticity is mediated in part by epigenetic mechanisms. However, recognition of the importance of developmental plasticity as an important factor in influencing later life health-particularly within the medical and public health communities-is low, and we argue that this indifference cannot be sustained in light of the growing understanding of developmental processes and the rapid rise in the prevalence of obesity and metabolic disease globally.
"Several lines of evidence suggest that this might be the case. These include the potential for the epigenome to mediate environmental influences (reviewed in Cortessis et al., 2012; Hou et al., 2012; Perera & Herbstman, 2011; Reamon-Buettner et al., 2008) or the maintenance of memory of events that occurred in the past, including prenatal exposures influencing adult disease susceptibility (reviewed in Barouki et al., 2012; Gluckman et al., 2011; Warner & Ozanne, 2010; Waterland & Michels, 2007). The field of cancer epigenomics has established a precedent for the silencing or activation of genes being causally involved in neoplasia (Dawson & Kouzarides, 2012; Esteller, 2007), somatic events that are usually limited to the cells or tissue in which the cancer arose, with a few notable exceptions (Cui et al., 2003; Gaston et al., 2001). "
[Show abstract][Hide abstract] ABSTRACT: Epigenetic dysregulation in disease is increasingly studied as a potential mediator of pathophysiology. The epigenetic events are believed to occur in somatic cells, but the limited changes of DNA methylation in studies to date indicate that only subsets of the cells tested undergo epigenetic dysregulation. The recognition of this subpopulation effect indicates the need for care in design and execution of epigenome-wide association studies (EWASs), paying particular attention to confounding sources of variability. To maximize the sensitivity of the EWASs, ideally, the cell type mediating the disease should be tested, which is not always practical or ethical in human subjects. The value of using accessible cells as surrogates for the target, disease-mediating cell type has not been rigorously tested to date. In this review, participants in a workshop convened by the National Institutes of Health update EWAS design and execution guidelines to reflect new insights in the field.
"In the current study, we observed a negative association between using solid fuels for heating or cooking before age 20 and global methylation in peripheral blood DNA. These data support the hypothesis that early-life exposure of air pollution may lead to persistent changes on DNA methylation, and further influence adult disease risk (Gluckman et al., 2011). Both animal models and human studies have shown that prenatal exposure to environmental contaminate or deficiency of certain nutrient is associated with subsequent IGF2 ICR methylation disruption, which may affect phenotype of the offspring (Wu et al., 2004; Heijmans et al., 2008; Kim et al., 2013). "
[Show abstract][Hide abstract] ABSTRACT: DNA methylation is a potential mechanism linking indoor air pollution to adverse health effects. Fetal and early-life environmental exposures have been associated with altered DNA methylation and play a critical role in progress of diseases in adulthood. We investigated whether exposure to indoor air pollution from solid fuels at different lifetime periods was associated with global DNA methylation and methylation at the IFG2/H19 imprinting control region (ICR) in a population-based sample of non-smoking women from Warsaw, Poland. Global methylation and IFG2/H19 ICR methylation were assessed in peripheral blood DNA from 42 non-smoking women with Luminometric Methylation Assay (LUMA) and quantitative pyrosequencing, respectively. Linear regression models were applied to estimate associations between indoor air pollution and DNA methylation in the blood. Compared to women without exposure, the levels of LUMA methylation for women who had ever exposed to both coal and wood were reduced 6.70% (95% CI: −13.36, −0.04). Using both coal and wood before age 20 was associated with 6.95% decreased LUMA methylation (95% CI: −13.79, −0.11). Further, the negative correlations were more significant with exposure to solid fuels for cooking before age 20. There were no clear associations between indoor solid fuels exposure before age 20 and through the lifetime and IFG2/H19 ICR methylation. Our study of non-smoking women supports the hypothesis that exposure to indoor air pollution from solid fuels, even early-life exposure, has the capacity to modify DNA methylation that can be detected in peripheral blood.
Environmental Research 10/2014; 134:325–330. DOI:10.1016/j.envres.2014.08.017 · 4.37 Impact Factor
"For instance, overweight and obesity are reaching epidemic proportions globally, and these are associated with morbidity and mortality due to cardiovascular diseases, diabetes and cancer at all levels—individual, family and population (Xavier Pi-Sunyer 2012; Aronne 2012). Diseases associated with obesity could influence suites of cardiac aging traits among the young and old alike, irrespective of the gender differences, and these may be contributing to cryptic evolutionary changes in contemporary human populations (Gluckman et al. 2011; Stearns et al. 2010; Kreiger et al. 2012; Perlman 2013). We suggest that the use of systems and causal analytical approaches in relation to human health will provide valuable insights to predict, prevent and postpone not only cardiac aging, thus improve general health of populations, but also to measure evolutionary changes in contemporary human populations. "
[Show abstract][Hide abstract] ABSTRACT: Aging process or senescence affects the expression of a wide range of phenotypic traits throughout the life span of organisms. These traits often show modular, synergistic, and even antagonistic relationships, and are also influenced by genomic, developmental, physiological and environmental factors. The cardiovascular system (CVS) in humans represents a major modular system in which the relationships among physiological, anatomical and morphological traits undergo continuous remodeling throughout the life span of an individual. Here we extend the concept of developmental plasticity in order to study the relationships among 14 traits measured on 3,412 individuals from the Framingham Heart Study cohort, relative to age and gender, using exploratory structural equation modeling-a form of systems analysis. Our results reveal differing patterns of association among cardiac traits in younger and older persons in both sexes, indicating that physiological and developmental factors may be channeled differentially in relation to age and gender during the remodeling process. We suggest that systems approaches are necessary in order to understand the coordinated functional relationships among traits of the CVS over the life course of individuals.
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