Metabolomics study by metabolite profiling analysis in kidney and liver of calorie-restricted aging rats using GC-MS/MS.

Aging leads to deterioration of the liver and kidney. Metabolic research on aging organs, including liver and kidney and metabolic studies of caloric restriction (CR), which delay aging and extends lifespan, are not well understood. In this study, we monitored metabolic changes associated with aging and explored potential biomarkers in kidney and liver of young (Y, 8 months), old (O, 23 months), and old calorie-restricted (OCR, 23 months) rats by metabolic profiling of organic acids (OA), free fatty acids (FFA), amino acids (AA) using gas chromatography-tandem mass spectrometry. Optimization of OA, FFA, and AA profiling methods were useful for quantifying these metabolites in kidney and liver. Profile analysis identified 48 and 45 metabolites in the kidney and liver, respectively. In the kidney, malic acid was significantly higher when comparing the Y and O groups, whereas 3-hydroxybutyric acid was significantly higher when comparing the O and OCR groups. In the liver, four metabolites (phenylacetic acid, valine, isoleucine, and tyrosine) were significantly evaluated as potential biomarker when comparing the Y and O groups, whereas 3-hydroxybutyric acid was significantly increased when comparing the O and OCR groups. Metabolomics results indicate that aging leads to mitochondrial dysfunction, phenylalanine metabolism disorders, and kidney dysfunction, whereas CR may regulate renal aging by reducing oxidative stress, inflammation, and lipid accumulation, while improving energy metabolism and resistance to oxidative stress in the liver. This result may explain some changes in the metabolism of aged kidney and liver during aging and CR.