Age-Related Changes in Sulfur Amino Acid Metabolism in Male C57BL/6 Mice

Abstract

Alterations in sulfur amino acid metabolism are associated with an increased risk of a number of common late-life diseases, which raises the possibility that metabolism of sulfur amino acids may change with age. The present study was conducted to understand the age-related changes in hepatic metabolism of sulfur amino acids in 2-, 6-, 18- and 30-month-old male C57BL/6 mice. For this purpose, metabolite profiling of sulfur amino acids from methionine to taurine or glutathione (GSH) was performed. The levels of sulfur amino acids and their metabolites were not significantly different among 2-, 6- and 18-month-old mice, except for plasma GSH and hepatic homocysteine. Plasma total GSH and hepatic total homocysteine levels were significantly higher in 2-month-old mice than those in the other age groups. In contrast, 30-month-old mice exhibited increased hepatic methionine and cysteine, compared with all other groups, but decreased hepatic S-adenosylmethionine (SAM), S-adenosylhomocysteine and homocysteine, relative to 2-month-old mice. No differences in hepatic reduced GSH, GSH disulfide, or taurine were observed. The hepatic changes in homocysteine and cysteine may be attributed to upregulation of cystathionine β-synthase and down-regulation of γ-glutamylcysteine ligase in the aged mice. The elevation of hepatic cysteine levels may be involved in the maintenance of hepatic GSH levels. The opposite changes of methionine and SAM suggest that the regulatory role of SAM in hepatic sulfur amino acid metabolism may be impaired in 30-month-old mice.

Effect of Endotoxemia Induced by Intraperitoneal Injection of Lipopolysaccharide on the Mg isotopic Composition of Biofluids and Tissues in Mice

“…Jeon et al reported a significant decrease with age in plasma glutathione and hepatic homocysteine levels when comparing 2, 6, and 18 months old C57BL/6 male mice. While the level of the other sulfur-containing amino acids were not different among those age groups, the concentration of sulfur-containing amino acids was significantly affected in the liver of 30-months old mice (49). Interestingly, we observed a significant increase in the total sulfur blood plasma concentration in aged mice (40-65 weeks) compared to young controls (14-28 weeks), suggesting that total plasma sulfur concentration is not an indicator of the status of sulfur-containing amino acids in blood plasma.…”

Cysteine restriction‐specific effects of sulfur amino acid restriction on lipid metabolism

“…Hence, using the same concentration of Met (0.12%) in the SAAR diet for adult mice might not result in the same level of restriction as in young. Aging alters the transsulfuration pathway, which could affect the magnitude of CR and CR‐specific changes (Jeon et al, 2018 ). Future studies should try SAAR diets with less than 0.12% Met to increase the efficacy in adult mice.…”

Beneficial Effects of Fermented Papaya Preparation (FPP®) Supplementation on Redox Balance and Aging in a Mouse Model

“…Similarly considering the redox balance, in ET-FPP ® mice we have much higher antioxidants levels and a greater reduction of ROS than in LT-FPP ® mice. The plasma levels of antioxidants, in particular GSH and SOD-1, usually decrease with increasing age [64][65][66][67], therefore in the case of LT-FPP ® mice, FPP ® induces an increase in GSH and SOD-1, but starting from lower basal levels, thus failing to trigger a minimally comparable anti-aging action.…”