Nutritional factors and gender influence age‐related DNA methylation in the human rectal mucosa

Abstract

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammation.

DNA methylation and healthy human aging

“…As the study of DNA methylation and aging develops, improvements in technology will begin to give us a better understanding of the genomic locations where these changes occur. For studies of epigenetic drift or the epigenetic clock, the integration of environmental exposures and health outcomes will be a particular challenge, though highly pertinent as exposures such as sun exposure and stress have already been shown to affect DNA methylation levels at age‐associated sites (Grönniger et al ., 2010; Tapp et al ., 2013; Boks et al ., 2014 Noreen et al ., 2014). …”

Patterns of DNA methylation in the normal colon vary by anatomical location, gender, and age

“…1,17 There is also evidence that the degree of methylation of certain genes in the normal colon varies between males and females. 18,19 A better understanding of variations in genome-wide methylation in the normal colon related to age, gender, and anatomical location is needed in order to identify methylated genes that are specifically associated with the development of neoplasia.…”

Epigenetic effects of selenium and their implications for health

“…18,38 A study with humans assessed the methylation status of colorectal cancer-related genes in healthy rectal mucosa specimens (84 males, 101 females) in relation to Se status. 39 An association was found for WIF1 (wnt inhibitory factor 1) methylation and plasma Se concentration. Interestingly, Se status was also associated with methylation of other genes and retrotransposons, including LINE1 (long interspersed nucleotide element 1), PCA1 (cation-transporting P-type ATPase), SFRP1/2 (secreted frizzled-related protein 1/2), and APC, and this occurred in a gender-specific manner.…”