Increased Sirtuin expression, senescence regulating miRNAs, mtDNA, and bifidobacteria correlate with wellbeing and skin appearance after sirtuin-activating drink

Abstract

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 (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.