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. 2016 Aug;15(4):755-65.
doi: 10.1111/acel.12485. Epub 2016 May 11.

Age-dependent Expression of DNMT1 and DNMT3B in PBMCs From a Large European Population Enrolled in the MARK-AGE Study

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Free PMC article

Age-dependent Expression of DNMT1 and DNMT3B in PBMCs From a Large European Population Enrolled in the MARK-AGE Study

Fabio Ciccarone et al. Aging Cell. .
Free PMC article

Abstract

Aging is associated with alterations in the content and patterns of DNA methylation virtually throughout the entire human lifespan. Reasons for these variations are not well understood. However, several lines of evidence suggest that the epigenetic instability in aging may be traced back to the alteration of the expression of DNA methyltransferases. Here, the association of the expression of DNA methyltransferases DNMT1 and DNMT3B with age has been analysed in the context of the MARK-AGE study, a large-scale cross-sectional study of the European general population. Using peripheral blood mononuclear cells, we assessed the variation of DNMT1 and DNMT3B gene expression in more than two thousand age-stratified women and men (35-75 years) recruited across eight European countries. Significant age-related changes were detected for both transcripts. The level of DNMT1 gradually dropped with aging but this was only observed up to the age of 64 years. By contrast, the expression of DNMT3B decreased linearly with increasing age and this association was particularly evident in females. We next attempted to trace the age-related changes of both transcripts to the influence of different variables that have an impact on changes of their expression in the population, including demographics, dietary and health habits, and clinical parameters. Our results indicate that age affects the expression of DNMT1 and DNMT3B as an almost independent variable in respect of all other variables evaluated.

Keywords: DNA methylation; DNMT1; DNMT3B; aging.

Figures

Figure 1
Figure 1
Age‐related changes of DNMT1 and DNMT3B mRNA levels with age in females and males from RASIG population. The picture shows a graphical representation of DNMT1 and DNMT3B mRNA as log‐transformed data vs. age in the RASIG sample. (A1) Dot plot of log‐transformed DNMT3B data vs. age in RASIG females; (A2) dot plot of log‐transformed DNMT3B data vs. age in RASIG males; (A3) dot plot of log‐transformed DNMT3B data vs. age in all RASIG samples; (B1) dot plot of log‐transformed DNMT1 data vs. age in RASIG females; (B2) dot plot of log‐transformed DNMT1 data vs. age in RASIG males; (B3) dot plot of log‐transformed DNMT1 data vs. age in all RASIG samples. Correlation coefficients (Pearson R for log‐transformed data and Spearman's rho for untransformed data) are noted below each graph. Significance and 95% confidence interval of correlation coefficients (within brackets) are estimated by bias‐corrected and accelerated (BCa) bootstrap with stratified sampling (1000 samples stratified for country, and also for gender when all data are used). R‐square and significance of the unique relevant quadratic regression is noted above panel B3. Graph and regression coefficients are also reported considering data of DNMT1 in the age range from 35 to 64 years in RASIG female (panel C1), in RASIG males (panel C2) as well as in all RASIG population (panel C3).
Figure 2
Figure 2
Levels of DNMT1 and DNMT3B mRNA in GO, SGO and RASIG. The picture shows a graphical representation of DNMT1 (A) and DNMT3B (B) mRNA level in PBMCs from GO, SGO and RASIG from the whole MARKAGE sample above 54 years. Analysis was performed in subjects above 54 years due to nonrepresentative numbers of GO and SGO below this age. **P < 0.01 from RASIG by post hoc (LSD) of GLM analysis and by KW test performed within each country.

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References

    1. Armstrong VL, Rakoczy S, Rojanathammanee L, Brown‐Borg HM (2013) Expression of DNA methyltransferases is influenced by growth hormone in the long‐living Ames dwarf mouse in vivo and in vitro. J. Gerontol. 69, 923–933. - PMC - PubMed
    1. Bacalini MG, Friso S, Olivieri F, Pirazzini C, Giuliani C, Capri M, Santoro A, Franceschi C, Garagnani P (2014) Present and future of anti‐ageing epigenetic diets. Mech. Ageing Dev. 136–137, 101–115. - PubMed
    1. Balada E, Ordi‐Ros J, Serrano‐Acedo S, Martinez‐Lostao L, Rosa‐Leyva M, Vilardell‐Tarres M (2008) Transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus. Immunology 124, 339–347. - PMC - PubMed
    1. Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkila J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W (2010) Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE 5, e10667. - PMC - PubMed
    1. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6–21. - PubMed

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