Biomolecules & Therapeutics  
Age-Related Changes in Sulfur Amino Acid Metabolism in Male C57bl/6 Mice
Jang Su Jeon1,†, Jeong-Ja Oh1,†, Hui Chan Kwak1,†, Hwi-yeol Yun1, Hyoung Chin Kim2, Young-Mi Kim3, Soo Jin Oh2,4,* and Sang Kyum Kim1,*
1College of Pharmacy, Chungnam National University, Daejeon 34134,
2Bio-Evaluation Center, KRIBB, Ochang 28116,
3College of Pharmacy, Hanyang University, Ansan 15588,
4New Drug Development Center, ASAN Institute for Life Science, Asan Medical Center, Seoul 05505, Republic of Korea
E-mail: sangkim@cnu.ac.kr (Kim SK), diatree@kribb.re.kr (Oh SJ)
Tel: +82-42-821-5930 (Kim SK), +82-43-240-6539 (Oh SJ)
Fax: +82-42-823-6566 (Kim SK), +82-43-240-6529 (Oh SJ)
The first three authors contributed equally to this work.
Received: March 7, 2017; Revised: March 30, 2017; Accepted: March 30, 2017; Published online: June 14, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

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.
Keywords: Aging, Mice, Sulfur amino acids, Metabolomics


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