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Background: Regular, especially sustained exercise training plays an important role in the prevention and treatment of multiple chronic diseases. Some of the underlying molecular and cellular mechanisms behind the adaptive response to physical activity are still unclear, but recent findings suggest a possible role of epigenetic mechanisms, especially miRNAs, in the progression and management of exercise related changes. Due to the combination of the analysis of epigenetic biomarkers (miRNAs), the intake of food and supplements, and genetic dispositions, a “fitness sore” was evaluated to assess the individual response to nutrition, metabolism and exercise.Methods: In response to a 12-week sport intervention we analyzed genetic and epigenetic biomarkers in capillary blood, including Line-1 methylation, three SNPs and ten miRNAs using HRM and qPCR analysis. These biomarkers were also analyzed in a control group without intervention. Food frequency intake, including dietary supplement intake, and general health questionnaires were surveyed under the supervision of trained staff.Results: Exercise training decreased the expression of miR-20a, -22 and -505 (p < 0.02) and improved the “fitness score”, which estimates eight different lifestyle factors to assess, nutrition, inflammation, cardiovascular fitness, injury risk, regeneration, muscle- and hydration status as well as stress level. In addition, we were able to determine correlations between individual miRNAs, miR-20a, -22 and -101 (p < 0.04), and the genetic predisposition for endurance and / or strength and for obesity risk (ACE, ACTN3 and FTO), as well as between miRNAs and the body composition (p < 0.05). And we identified two miRNAs, miR-19b and -378a (p < 0.05), which could potentially provide information about the micronutrient / vitamin requirements of an athlete.Conclusions: Due to the detailed knowledge of individual regulatory mechanisms in the metabolism of sport intervention and / or nutritional behavior, this knowledge and our results can be used for personalized interventions and in the context of the new field of precision nutrition and precision training.

The main argument for the optimization of nutritional strategies in athletes, besides improved performance, is the preservation of health and the prevention of unwanted training effects. This highlights the importance of personalized nutrition strategies, as well as functional foods and phytonutrients based on individual requirements which can be precisely defined by detailed analyses, including genetics, epigenetics, gut microbiota, gender, and environmental factors. Recently, a miRNA-based “Fitness Score to Assess the Individual Response to Diet, Metabolism and Exercise” was developed by our group. Formulations of sports drinks and sports foods should be carefully considered, as they frequently contain a mixture of multiple ingredients. Macronutrient supplements, such as carbohydrates, proteins, protein components, fatty acids and probiotics are known to provide benefits for athletes with energy deficits, electrolyte imbalance, gastrointestinal issues, fatigue, and cardiovascular problems. However, micronutrient supplements, such as vitamins, minerals, trace elements and ergogenic aids (e.g., caffeine) must be administered in specific doses based on individual need. Considering the novel data on inter-organ communication (e.g., gut-muscle-brain-axis), data from systems biology highlight the importance of holistic aspects, where nutrients and probiotic supplements are gaining importance for improved performance, reduced risks of illness/ injury and enhanced recovery.Keywords: Nutrition, additives, functional foods, exercise, microbiome, epigenetics, personalization

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 and was shown to interact with SIRT pathways. This study investigated the effects of a drink containing a mix of different SPIs in combination with galactooligosaccharides (G OS) 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

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 H 2 O 2 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

Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans.