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Metabolomics study by metabolite profiling analysis in kidney and liver of calorie-restricted aging rats using
Byeongchan Choi1, Moongi Ji1, Jaeyeop Lim1
1College of Pharmacy, Sunchon National University, Suncheon 57922, Republic of Korea.
Abstract:
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.
Insights
Aging impairs liver and kidney function, but caloric restriction (CR) shows promise. Metabolomics reveals key biomarkers and suggests CR combats aging by reducing oxidative stress and inflammation, improving metabolism.
Area of Science:
- Gerontology
- Metabolomics
- Organ Physiology
Background:
- Aging causes liver and kidney deterioration, with limited understanding of metabolic changes.
- Caloric restriction (CR) is known to delay aging and extend lifespan, but its metabolic effects on aging organs are not well understood.
Purpose of the Study:
- To monitor metabolic changes in aging rat kidneys and livers.
- To identify potential metabolic biomarkers of aging and CR in these organs.
Main Methods:
- Metabolic profiling of organic acids (OA), free fatty acids (FFA), and amino acids (AA) in young, old, and old calorie-restricted rat kidneys and livers.
- Gas chromatography-tandem mass spectrometry (GC-MS/MS) was employed for metabolite quantification.
Main Results:
- Identified 48 kidney and 45 liver metabolites. Key kidney changes included higher malic acid in old vs. young rats and higher 3-hydroxybutyric acid in old vs. old calorie-restricted rats.
- Liver analysis revealed significant differences in phenylacetic acid, valine, isoleucine, and tyrosine between young and old rats, and increased 3-hydroxybutyric acid in old vs. old calorie-restricted rats.
- Metabolomics indicated aging-induced mitochondrial dysfunction, phenylalanine metabolism disruption, and kidney dysfunction, while CR mitigated these effects.
Conclusions:
- Aging significantly alters kidney and liver metabolism, impacting mitochondrial function and amino acid pathways.
- Caloric restriction may protect against renal aging by reducing oxidative stress, inflammation, and lipid accumulation.
- CR appears to improve liver energy metabolism and oxidative stress resistance, offering insights into aging and CR interventions.
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