| Purpose: The aim of this work was to investigate the metabolic trajectory of kidney aging,and the effects of Polygonatum sibiricum polysaccharides(PSP)against kidney aging in D-galactose induced aging mice,based on ultra-performance liquid chromatography/ Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive MS/MS).Methods: A widely used aging and anti-aging model induced by D‐galactose(D‐gal)was establish on C57 BL/6J mice.Key markers of renal function in urine and serum,such as creatinine(Crea),urea nitrogen(BUN)and uric acid(UA)levels were determined to validate the successful establishment of kidney aging models,and estimated the effects of PSP.HE staining,PAS staining and β-galactosidase staining were used to assess the renal pathological changes.The metabolic profiles of serum,kidney,and urine samples from different groups were analyzed by UPLC-Q-Exactive MS/MS,and pattern recognition methods were used to outline metabolic trajectory of kidney aging,and identification of characteristic metabolites.Results: PSP improved kidney functions and oxidative stress,and significantly ameliorated renal pathological damage in aging mice.Meanwhile,the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis,and were further analyzed to form related metabolic pathways.The results showed that purine metabolism,sphingolipid metabolism,glycerophospholipid metabolism,tryptophan metabolism and riboflavin metabolism were the main features of aging.After administration of PSP,these pathological indexes were adjusted to normal levels,and biomarkers related to the aging process,such as adenosine monophosphate(AMP),tryptophan,and 5-hydroxytryptophan,were also shown to be somewhat back-regulated.Conclusion: Metabolomics methods based on LC-MS/MS and multivariate statistical analysis can be used for establishing metabolic profiling of aging mice.According to our results,PSP appears protective effects against kidney aging through interfere the purine metabolism,sphingolipid metabolism,glycerophospholipid metabolism,tryptophan metabolism and riboflavin metabolism in the kidney. |