Fasting and fasting mimetic supplementation address sirtuin expression, miRNA and microbiota composition

Abstract

Background: Fasting and fasting mimetics - bioactive compounds mimicking fasting effects, are of growing interest as potential means to slow down the aging process and increase health span. Sirtuins are known as enzymes that interfere with mitochondrial energy metabolism and molecular pathways involved in longevity. Although their activation is determined as a response to stress i.e. caloric restriction. Sirtuin activating nutraceuticals are believed to mimic the effects of nutrient deprivation, thus activating signaling pathways correlated to an improved health span. In this study, we compare 5 days periodic buchinger fasting intervention with 3 months shot supplementation, a drink formula, containing secondary plant ingredients considered to activate sirtuins.Methods: We analyzed pathways in response to fasting and a sirtuins activating drink. Genetic and epigenetic biomarkers including telomere length, LINE1 methylation, and a set of mRNAs and miRNAs were assessed using qPCR analysis. Gut composition and metabolites were compared using Illumnia sequencing and mass spectrometry.Results: Fasting, but also the fasting mimetic could increase expression of FoxO1, SIRT1, and MLH1 mRNA, all genes discussed in aspects of longevity. A positive correlation between telomere length and both SIRT1, and SIRT6 was observed. Furthermore, a significant change in the gut composition was measured. Actinobacteria increased in the supplementation group, whereas after buchinger fasting a rise in the distribution of Proteobacteria could be observed. Firmicutes/Bacteroidetes ratio decreased and correlated with the body mass index (BMI).Conclusions: Our results confirm the effects of fasting on longevity associated mechanisms but also suggest that SIRTFOOD shot intervention addresses some of these effects.