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 Health Service Medical Center, Veterans Medical Research Institute, Seoul, South Korea.
Department of Internal Medicine, Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
J Cachexia Sarcopenia Muscle. 2024 Dec;15(6):2476-2486. doi: 10.1002/jcsm.13582. Epub 2024 Sep 4.
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.
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.
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).
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.
肌肉减少症是一种与年龄相关的肌肉质量和功能的渐进性丧失。肌肉减少症是一种多因素疾病，包括代谢紊乱；因此，代谢物可用作肌肉减少症的循环生物标志物。我们旨在使用代谢组学研究肌肉减少症的潜在生物标志物。
对肌肉减少症衰老小鼠模型的小鼠血浆进行非靶向代谢组分析后，使用靶向代谢组分析评估动物模型中的鞘脂代谢物和肌肉细胞。在年龄匹配的发现队列（72例病例和72例对照）和验证队列（36例病例和128例对照）中评估从小鼠和细胞研究中鉴定出的鞘脂代谢物与肌肉减少症状态之间的关联；患有肌肉减少症的女性（36例病例和36例对照）也作为发现队列纳入。
实验研究中的非靶向和靶向代谢组分析均显示鞘脂代谢物（包括神经酰胺（CERs）和鞘磷脂（SMs））与肌肉减少症之间存在关联。发现队列中患有肌肉减少症的男性血浆SM（16:0）、CER（24:1）和SM（24:1）水平显著高于对照组（所有P<0.05）。患有或未患有肌肉减少症的女性血浆鞘脂水平无显著差异。在发现队列的男性中，SM（16:0）用于低肌肉力量和低肌肉质量的受试者工作特征曲线下面积（AUROC）分别为0.600（95%置信区间[CI]：0.501-0.699）和0.647（95%CI：0.557-0.737）。男性中CER（24:1）和SM（24:1）用于低肌肉质量的AUROC（95%CI）分别为0.669（95%CI：0.581-0.757）和0.670（95%CI：0.582-0.759）。使用结合CER（24:1）和SM（16:0）水平的回归方程计算鞘脂（SphL）评分；SphL评分用于肌肉减少症的AUROC为0.712（95%CI：0.626-0.798）。在发现队列中，将SphL评分添加到握力（HGS）中显著提高了AUC，从0.646（95%CI：0.575-0.717；仅HGS）提高到0.751（95%CI：0.671-0.831，P=0.002；HGS+SphL）。在验证队列中证实了SphL评分对肌肉减少症的预测能力（AUROC=0.695，95%CI：0.591-0.799）。
反映低肌肉力量的SM（16:0）以及反映低肌肉质量的CER（24:1）和SM（16:0）是男性肌肉减少症的潜在循环生物标志物。需要对鞘脂代谢物进行进一步研究以证实这些结果，并为与肌肉减少症发病机制和诊断相关的代谢组学变化提供更多见解。
