Sodium rutin extends lifespan and health span in mice including positive impacts on liver health

Abstract

Background and purpose Aging is associated with progressive metabolic dysregulation. Rutin has reported as a metabolic regulating chemical with a poor solubility. At present, we use Na‐Rutin investigating the effect and mechanisms of rutin in aging process. Experimental approach Wildtype male mice were treated with or without NaR at the dosage of 0.2mg/ml in drinking water from 8‐month‐old until life end or sacrificed as indicated. Kaplan‐Meier survival curve were used for lifespan assay, aging‐related histopathology analysis and metabolic analysis were performed to determine the effects of chronic NaR treatment on the longevity. Serological test, liver tissue metabolomics and transcriptomics were used for liver function assay. SiRNA knockdown Angptl8 and autophagy flux assay in HepG2 cell lines, explored the mechanism through which NaR might impact the function of hepatocyte. Key results NaR treatment extends the lifespan of mice by 10%. NaR supplementation alleviates aging‐related pathological changes and promotes behavior performance in aging mice. NaR supplementation altered the whole‐body metabolism in mice, which exhibited an increased energy expenditure, lower respiratory quotient. Transcriptomics analysis showed that NaR affected the expression of metabolic genes. Metabolomics analysis showed that NaR reduced liver steatosis through increased lipid β‐oxidation. NaR treatment increased autophagy level both in vivo and in vitro. The inhibition of autophagy partially abolished the NaR‐mediated effect on lipolysis in HepG2 cells. Conclusion and implications NaR treatment extends the life‐ and healthspan of mice, the beneficial effects of NaR on metabolism were achieved by enhancing autophagy activity in hepatocytes.