Research Paper|Volume 14, Issue 5|pp 2101—2112

Pathway-based metabolomics study of sarcopenia-related traits in two US cohorts

Qi Zhao¹, Hui Shen², Jiawang Liu^3,⁴, Chi-Yang Chiu¹, Kuan-Jui Su², Qing Tian², David Kakhniashvili⁵, Chuan Qiu², Lan-Juan Zhao², Zhe Luo², Hong-Wen Deng²

¹Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
²Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA
³Medicinal Chemistry Core, Office of Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA
⁴Department of Pharmaceutical Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA
⁵Proteomics and Metabolomics Core, Office of Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA

* Equal contribution

Received: July 30, 2021Accepted: January 25, 2022Published: March 2, 2022

https://doi.org/10.18632/aging.203926

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.

Abstract

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.