한빛사논문
Je Hyun Seo1, Jung-Min Koh2, Han Jin Cho3, Hanjun Kim3, Young-Sun Lee3, Su Jung Kim4, Pil Whan Yoon5, Won Kim6, Sung Jin Bae7, Hong-Kyu Kim7, Hyun Ju Yoo4* & Seung Hun Lee2*
1Veterans Health Service Medical Center, Veterans Medical Research Institute, Seoul, South Korea;
2Department of Internal Medicine, Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;
3Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea;
4Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;
5Department of Orthopedic Surgery, Seoul Now Hospital, Anyang, South Korea;
6Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;
7Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
*Correspondence to: Hyun Ju Yoo, Seung Hun Lee
Je Hyun Seo and Jung-Min Koh are joint first authors.
Hyun Ju Yoo and Seung Hun Lee are joint corresponding authors.
Abstract
Background: Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics.
Methods: After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort.
Results: Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799).
Conclusions: SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.
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