Objective: In our previous studies on the anti-aging effects of ursolic acid (UA) on various tissues including skeletal muscle, heart, hypothalamus and pancreas, the protective and anti-aging roles of UA on renal tissue remained elusive. In this study, we aim to address this issue.

Materials and Methods: In this research we used 20 aged male mice C57/BL6. After optimizing the conditions for treatment, UA was dissolved in corn oil and administrated with 200 mg/kg doses twice a day for 7 days in the form of intra-peritoneal injection. The animals were anaesthetized and perfused in order to analyze the tissues through Immunofluorescence (IF) and histochemical tests.

Results: The findings showed that UA significantly increased SIRT1 (~ 4 folds), p<0.001. Furthermore, UA enhanced SIRT6 up-regulation (~ 5 folds), p<0.001. With regard to the prominent role of α-Klotho in the control of CKD progression, our findings obviously showed that UA enhanced α-Klotho expression (~ 3.51 folds), p<0.001.

Conclusions: By enhancing SIRT1 expression, it seems that UA may be a new therapeutic agent to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. It led to a decrease in glomerular cell apoptosis, inflammation, sodium reabsorption, blood pressure, and interstitial fibrosis, and an increase in autophagy and renal lipid metabolism. Also, enhancing of SIRT6 in the kidney of aged mice using UA promotes metabolism regulation, DNA repair and longevity. Finally, through up-regulation of α-Klotho, UA prohibits the kidney vulnerability, renal fibrosis and induces kidney regeneration.