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EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

Angelika Pointner, Ulrich Magnet, Elena Tomeva, Elisabeth Dum, Christina Bruckmueller, Christine Mayer, Eva Aumueller and Alexander Haslberger

Objective: In vitro and in vivo studies in rodents have demonstrated many health promoting properties of individual phytochemicals including antioxidative and chemopreventive effects. Recently combination of substances is claimed to enhance activity. The objective of this study was to investigate health benefits of a daily consumption of a combination of a large variety of phytochemicals (TimeBlock®). To assess potential changes we analyzed specific biomarkers that are associated with aging, oxidative stress and DNA stability: Methylation of LINE-1, c-Myc, IL-6, MLH1, DNTM1, ITGA2B and telomere length. Methods: For this study 110 healthy participants of both sexes between 31-76 years were recruited, 101 subjects were included in further analysis. A small reference group (n=20) without intervention within the same age interval served as control. Participants received a plant based dietary supplement (TimeBlock®) for 6 months by oral administration. Ingredients included extracts from green tea (EGCG), wheatgrass (tocotrienols), barley grass (folic acid), tomatoes (lycopene), tagetes (zeaxanthin, lutein), algae, shiitake mushrooms (vitamin D) and grape seeds (resveratrol). Capillary blood samples were collected from all participants before administration and within 6 days after the end of the study period following DNA extraction, bisulfite conversion and qPCR as well as high resolution melting curve analysis addressing analysis of LINE-1, c-Myc, IL-6, MLH1, DNTM1, ITGA2B and telomere length. Nutrition, lifestyle and health status were assessed with a standardized food and lifestyle questionnaire. Results and discussion: Our results confirmed the positive effect of plant derived antioxidants on telomeres and inflammation frequency. An age-specific drift of analyzed markers could be observed. While methylation of c-Myc-a key factor in telomerase regulation-was not affected by administration, total telomere length showed a significant increase, which we suggest to be linked with an increased cell turnover and accelerated apoptosis of senescent or mutated cells without enhancing telomerase activity. Further, methylation of mismatch repair protein gene MLH1 showed a strong negative correlation with telomere length, supporting the influence of MMR on telomere regulation. Conclusion: The results of the present study indicate that a combined administration of a variety of phytochemicals can be a potential preventive and therapeutic agent, as each substance exhibits different modes of action and in combination, health promoting effects could be potentiated. Addressing different mechanisms of aging, specific phytochemicals could be used as new therapeutic approach against age-related diseases.