BackgroundOxidative stress may lead to an increased level of unrepaired cellular DNA damage, which is discussed as one risk for tumor initiation. Mismatch repair (MMR) enzymes act as proofreading complexes that maintain the genomic integrity and MMR-deficient cells show an increased mutation rate. One important gene in the MMR complex is the MutL homolog 1 (MLH1) gene. Since a diet rich in antioxidants has the potential to counteract harmful effects by reactive oxygen species (ROS), we investigated the impact of an antioxidant, folate, and vitamin rich diet on the epigenetic pattern of MLH1. These effects were analyzed in individuals with non-insulin depended diabetes mellitus type 2 (NIDDM2) and impaired fasting glucose (IFG).MethodsIn this post-hoc analysis of a randomized trial we analyzed DNA methylation of MLH1, MSH2, and MGMT at baseline and after 8 weeks of intervention, consisting of 300 g vegetables and 25 ml plant oil rich in polyunsaturated fatty acids per day. DNA methylation was quantified using combined bisulfite restriction enzyme analysis (COBRA) and pyrosequencing. MLH1 and DNMT1 mRNA expression were investigated by qRT-PCR. DNA damage was assessed by COMET assay. Student’s two-tailed paired t test and one-way ANOVA with Scheffé corrected Post hoc test was used to determine significant methylation and expression differences. Two-tailed Pearson test was used to determine correlations between methylation level, gene expression, and DNA strand break amount.ResultsThe intervention resulted in significantly higher CpG methylation in two particular MLH1 promoter regions and the MGMT promoter. DNA strand breaks and methylation levels correlated significantly. The expression of MLH1, DNMT1, and the promoter methylation of MSH2 remained stable. CpG methylation levels and gene expression did not correlate.ConclusionThis vitamin and antioxidant rich diet affected the CpG methylation of MLH1. The higher methylation might be a result of the ROS scavenging antioxidant rich diet, leading to lower activity of DNA demethylating enzymes. Our results suggest the hypothesis of CpG demethylation via DNA repair enzymes under these circumstances. NIDDM2 and IFG patients benefit from this simple dietary intervention involving epigenetic and DNA repair mechanisms.

The microbiota-gut-brain axis is a bidirectional homeostatic route of communication between both of the organs direct via receptors of the CNS or via epigenetic mechanisms of divers metabolites e.g. SCFA, GABA, β-hydroxybutyrate. Thus, a modulation of gut microbiota via nutrition, lifestyle etc. might be effective for emotional status and depressive disorders. The dietary composition has an influence on gut microbiota composition, microbial metabolite profile and the according consequences on emotional status and depression within a system biologic approach. There are changes in gut microbiota composition and gut microbial profile (butyrate, GABA, β-hydroxybutyrate) effecting epigenetic regulation (histone acetylation, DNA methylation) and gene expression of receptors and mediators (SLC6A4, BDNF, GABA, GPRs) involved in depressive disorders.

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Introduction: Obesity is a multifactorial condition that results from the interactions among genetic, dietary, environmental, and lifestyle factors. In our study, we have employed a novel integrative approach to identify mechanisms involved in human disease. Method: In contrast to previous methodologies employed for integration of heterogeneous OMIC data, we based the integration on genomic positions of alterations in human disease. A data search for various types of studies on obesity (genome-wide association, meta-analysis, transcriptomic, proteomic studies and epigenetic studies) was conducted in literature sources and OMIC data repositories, using GWAS Central and Medline database with search string (obesity) AND (transcriptome OR proteome OR genome-wide OR microarray OR profiling OR epigenetics). Additionally, Gene Expression Omnibus (GEO) repository, Array Express and Stanford Microarray Database were searched to discover suitable sources of data for inclusion in our initial dataset. Results and Discussion: As a result of the employed high through put technology, 71 high scoring regions were identified. We identified 8 high scoring gene regions (ATP5O, ALK7, CR1, CR2, S100, GAPDH, TLR1 and TLR6) that have not yet been associated to obesity. Interestingly, all of these genes were identified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes to be implicated in the energy metabolism and the immune response, which are known to be involved in obesity. Conclusion: In our study, we have performed a novel integrative approach to identify candidate regions and genes involved in human disease. The results showed that none of the high scoring genes that were identified were yet associated with obesity per se, but that they were found to be implicated in the immune response or the energy metabolism. Further research will be needed to validate the found gene regions for obesity.

Introduction: Topical investigations have demonstrated that oxidative stress and inflammation play key roles in biological aging and determine incidence and course of age-related diseases. Lifestyle and environmental factors hugely impact epigenetic regulation and DNA stability with telomere attrition and epigenetic instability providing a potential record of the cumulative burden of endogenous and exogenous oxidative noxae. Certain physiologically active plant components exhibit antioxidative activities affecting epigenetic regulation of inflammation response and DNA repair.Methods: Against this background, the present study investigated green tea polyphenol epigallocatechin gallate (EGCG) in the context of telomere regulation in Caco-2 colorectal adenocarcinoma cells vs. ES-1 primary skin fibroblasts. Cell lines were treated with 20 and 200 µM EGCG for 36, 72 and 144 hours, respectively. Telomerase activity, relative telomere length as well as methylation status of hTERT and c-Myc from different culture conditions were assessed. Malondialdehyde (MDA) served as a surrogate marker of potential pro-oxidative effects of EGCG in a physiologically relevant tissue model.Results: EGCG incubation was associated with telomere shortening and decreased telomerase activity in Caco-2 cells, and relatively longer telomeres along with increased methylation of six 5'—C—phosphate—G—3' (CpG) sites in the promoter region of human Telomerase Reverse Transcriptase (hTERT) in fibroblasts. At low concentrations, EGCG significantly decreased oxidative damage to lipids in Caco-2 cells and attenuated H2O2 induced oxidation at higher concentrations.Conclusion: These results suggest differential EGCG-mediated telomeric modulation in cancer vs. primary cells and a specific antioxidant activity of EGCG against oxidative damage to lipids in abnormal cells.Keywords: Caco-2, epigallocatechin gallate, telomeres, hTERT, DNA methylation, telomerase, oxidative stress, malondialdehyde

Background: In recent years, more and more evidence has accumulated to elucidate the modulating roles of microRNA in immune and inflammatory system. We conducted a novel positional omics integration study to identify microRNAs that could shed further light on the possible links between microRNAs, adipose tissue immunity/inflammation and obesity.

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Background: Sirtuins attract high attention considering their properties to reverse molecular hallmarks of aging and age-related disorders. Many secondary plant ingredients (SPI) are known for their sirtuin-activating activities as well as epigenetic regulation of telomers, autophagy, senolysis, DNA repair but also improvement of gut microbiota. Furthermore, prebiotics enhanced butyrate was shown to interact with SIRT pathways. This study investigated effects of a drink containing a mix of different SPIs in combination with galactooligosaccharides (GOS) and their effect on SIRT activation, markers of aging relevant mechanisms and gut microbiota composition in correlation with subjective wellbeing and skin structure appearance. Methods: We analyzed gene expression, mtDNA amount, and microbial composition in response to a sirtuin-activating drink in humans compared to a control group consuming a placebo. Food frequency, beauty, and general health questionnaires were asked, and a set of mRNAs and miRNAs were assessed using qPCR analysis. The gut composition was analyzed using Illumnia sequencing.Results: SPI increased SIRT1, SIRT3 and modulated cell cycle relevant miR16 and senescence regulating miR34 expression. Additionally, mtDNA amount was higher in the group consuming the active supplement indicating an improved mitochondrial activity. The combined effect of SPI and GOS lead to an increase of Actinobacteria, especially Bifidobacterium, but also Veillonellaceae which was not observed in the control group. Significant correlations between SIRT3 expression and the gut microbiota Bifidobacterium and Veillonellaceae were observed. Additionally, statistical analysis of subjects self-reporting indicated beneficial effects regarding beauty and wellbeing.Conclusion: Our results show that the combination of sirtuins inducing SPI and prebiotic GOS influences molecular pathways counteracting aging, senescence, inflammation, and enhanced groups of gut microbiota which are known to improve the innate and adaptive immune system. Keywords: secondary plant ingredients, prebiotic, Sirtuins, subjective wellbeing, Bifidobacterium