Research Paper Volume 14, Issue 5 pp 2101—2112
Pathway-based metabolomics study of sarcopenia-related traits in two US cohorts
- 1 Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
- 2 Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA
- 3 Medicinal Chemistry Core, Office of Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA
- 4 Department of Pharmaceutical Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA
- 5 Proteomics and Metabolomics Core, Office of Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Received: July 30, 2021 Accepted: January 25, 2022 Published: March 2, 2022https://doi.org/10.18632/aging.203926
How to Cite
Copyright: © 2022 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
We aimed to validate two metabolites, aspartic acid and glutamic acid, which were associated with sarcopenia-related traits, muscle mass and strength, in our previous untargeted metabolomics study and to identify novel metabolites from five metabolic pathways involving these two metabolites. We included a discovery cohort of 136 white women aged 20-40 years (used for the previous untargeted metabolomics analysis) and a validation cohort of 174 subjects aged ≥ 60 years, including men and women of white and black. A targeted LC-MS assay successfully detected 12 important metabolites from these pathways. Aspartic acid was associated with muscle mass and strength in the discovery cohort, but not in the validation cohort. However, glutamic acid was associated with these sarcopenia traits in both cohorts. Additionally, N-acetyl-L-aspartic acid and carnosine were the newly identified metabolites that were associated with muscle strength in the discovery and validation cohorts, respectively. We did not observe any significant sex and race differences in the associations of these metabolites with sarcopenia traits in the validation cohort. Our findings indicated that glutamic acid might be consistently associated with sarcopenia-related traits across age, sex, and race. They also suggested that age-specific metabolites and metabolic pathways might be involved in muscle regulation.
ALM: appendicular lean mass; BMI: body mass index; FDR: false discovery rate; HGS: hand grip strength; HMDB: Human Metabolome Database; HPLC: high performance liquid chromatography; ICD: International Classification of Diseases; KEGG: Kyoto Encyclopedia of Genes and Genomes; LC-MS: liquid chromatography-mass spectrometry; LOS: Louisiana Osteoporosis Study; MASS: MetAbolomics Study of Sarcopenia (MASS); NAA: N-acetyl-L-aspartic acid.