Seo Je Hyun, Koh Jung-Min, Cho Han Jin, Kim Hanjun, Lee Young-Sun, Kim Su Jung, Yoon Pil Whan, Kim Won, Bae Sung Jin, Kim Hong-Kyu, Yoo Hyun Ju, Lee Seung Hun
Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Endocrinol Metab (Seoul). 2025 Feb;40(1):93-102. doi: 10.3803/EnM.2024.2117. Epub 2024 Nov 28.
Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia.
Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort.
An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027).
C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.
肌肉减少症是一种涉及代谢紊乱的多因素疾病,提示存在代谢物生物标志物的可能性。肉碱(CN)对骨骼肌能量代谢至关重要,可能是一种候选生物标志物。我们研究了CN代谢物是否为肌肉减少症的生物标志物。
在年龄匹配的发现队列(72例病例,72例对照)和验证队列(21例病例,47例对照)的男性中,评估从肌肉减少症动物模型和肌肉细胞中鉴定出的CN代谢物与肌肉减少症状态之间的关联。
在小鼠和细胞研究中显示CN代谢物与肌肉减少症之间存在关联。在发现队列中,肌肉减少症男性的血浆C5-CN水平较低(P = 0.005)。男性的C5-CN水平倾向于与握力(HGS)相关(P = 0.098),并与骨骼肌质量显著相关(P = 0.003)。C5-CN水平每增加一个标准差,低肌肉质量的几率降低(比值比,0.61;95%置信区间[CI],0.42至0.89)。使用C5-CN水平回归方程的CN评分对肌肉减少症的受试者工作特征曲线下面积(AUROC)为0.635(95%CI,0.544至0.726)。在发现队列中,将CN评分添加到HGS中可使AUROC从0.646(95%CI,0.575至0.717;仅HGS)显著提高至0.727(95%CI,0.643至0.810;P = 0.006;HGS + CN评分)。在验证队列中也证实了这种改善(HGS的AUROC = 0.563;95%CI,0.470至0.656;HGS + CN评分的AUROC = 0.712;95%CI,0.569至0.855;P = 0.027)。
C5-CN可指示低肌肉质量,是男性肌肉减少症的一种潜在循环生物标志物。需要进一步研究来证实这些结果并探索与肌肉减少症相关的代谢组学变化。