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

BACKGROUND AND PURPOSE Ageing is associated with progressive metabolic dysregulation. Rutin is a metabolic regulator with a poor solubility. Using soluble sodium rutin we investigating the effect and mechanisms of rutin in ageing process. EXPERIMENTAL APPROACH Wild type male mice were treated with or without sodium rutin ( 0.2 mg·ml-1 in drinking water from 8-month-old until end of life. Kaplan-Meier survival curve was used for lifespan assay, ageing-related histopathology analysis and metabolic analysis were performed to determine the effects of chronic sodium rutin 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 sodium rutin might impact the function of hepatocyte. KEY RESULTS Sodium rutin treatment extends the lifespan of mice by 10%. Sodium rutin supplementation alleviates ageing-related pathological changes and promotes behaviour performance in ageing mice. Sodium rutin supplementation altered the whole-body metabolism in mice, which exhibited increased energy expenditure and lower respiratory quotient. Transcriptomics analysis showed that Sodium rutin affected the expression of metabolic genes. Metabolomics analysis showed that Sodium rutin reduced liver steatosis through increased lipid β-oxidation. Sodium rutin treatment increased the autophagy level both in vivo and in vitro. The inhibition of autophagy partially abolished the sodium rutin-mediated effect on lipolysis in HepG2 cells. CONCLUSION AND IMPLICATIONS Sodium rutin treatment extends the lifespan and health span of mice with beneficial effects on metabolism, which were achieved by enhancing the autophagy activity in hepatocytes.