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探索老年男性严重肌肉减少症生物标志物的代谢组学特征:一项初步研究。

Metabolomic profiles to explore biomarkers of severe sarcopenia in older men: A pilot study.

机构信息

Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, South Korea.

Elderly Frailty Research Center, Department of Family Medicine, College of Medicine, Kyung Hee University, Kyung Hee University Medical Center, Seoul 02447, South Korea.

出版信息

Exp Gerontol. 2022 Oct 1;167:111924. doi: 10.1016/j.exger.2022.111924. Epub 2022 Aug 10.

DOI:10.1016/j.exger.2022.111924
PMID:35963453
Abstract

BACKGROUND

The pathophysiology of sarcopenia is complex and multifactorial; however, it has not yet been fully elucidated. Identifying metabolomic profiles may help clarify the mechanisms underlying sarcopenia.

OBJECTIVE

This pilot study explored potential noninvasive biomarkers of severe sarcopenia through metabolomic analysis in community-dwelling older men.

METHODS

Twenty older men (mean age: 81.9 ± 2.8 years) were selected from the Korean Frailty and Aging Cohort Study. Participants with severe sarcopenia (n = 10) were compared with non-sarcopenic, age- and body mass index-matched controls (n = 10). Severe sarcopenia was defined as low muscle mass, low muscle strength, and low physical performance using the Asian Working Group for Sarcopenia 2019 criteria. Non-targeted metabolomic profiling of plasma metabolites was performed using capillary electrophoresis time-of-flight mass spectrometry and absolute quantification was performed in target metabolites.

RESULTS

Among 191 plasma metabolic peaks, the concentrations of 10 metabolites significantly differed between severe sarcopenia group and non-sarcopenic controls. The plasma concentrations of L-alanine, homocitrulline, N-acetylserine, gluconic acid, N-acetylalanine, proline, and sulfotyrosine were higher, while those of 4-methyl-2-oxovaleric acid, 3-methyl-2-oxovaleric acid, and tryptophan were lower in participants with severe sarcopenia than in non-sarcopenic controls (all, p < 0.05). Among the 53 metabolites quantified as target metabolites, L-alanine (area under the receiver operating characteristic curve [AUC] = 0.760; p = 0.049), gluconic acid (AUC = 0.800; p = 0.023), proline (AUC = 0.785; p = 0.031), and tryptophan (AUC = 0.800; p = 0.023) determined the presence of severe sarcopenia.

CONCLUSIONS

Plasma metabolomic analysis demonstrated that L-alanine, gluconic acid, proline, and tryptophan may be potential biomarkers of severe sarcopenia. The identified metabolites can provide new insights into the underlying pathophysiology of severe sarcopenia and serve as the basis for preventive interventions.

摘要

背景

肌少症的病理生理学复杂且多因素,但尚未完全阐明。确定代谢组学特征可能有助于阐明肌少症的发病机制。

目的

本研究通过代谢组学分析,探讨社区居住的老年男性严重肌少症的潜在无创生物标志物。

方法

从韩国虚弱与衰老队列研究中选择 20 名老年男性(平均年龄:81.9±2.8 岁)。根据 2019 年亚洲肌少症工作组标准,将患有严重肌少症(n=10)的患者与非肌少症、年龄和体重指数匹配的对照组(n=10)进行比较。严重肌少症定义为肌肉质量低、肌肉力量低和身体表现低。使用毛细管电泳飞行时间质谱对血浆代谢物进行非靶向代谢组学分析,并对靶代谢物进行绝对定量。

结果

在 191 个血浆代谢峰中,10 种代谢物的浓度在严重肌少症组和非肌少症对照组之间有显著差异。与非肌少症对照组相比,严重肌少症组患者的血浆 L-丙氨酸、同型瓜氨酸、N-乙酰丝氨酸、葡萄糖酸、N-乙酰丙氨酸、脯氨酸和硫酸酪氨酸浓度较高,而 4-甲基-2-氧代戊酸、3-甲基-2-氧代戊酸和色氨酸浓度较低(均,p<0.05)。在定量为 53 种代谢物的靶代谢物中,L-丙氨酸(受试者工作特征曲线下面积 [AUC] = 0.760;p=0.049)、葡萄糖酸(AUC = 0.800;p=0.023)、脯氨酸(AUC = 0.785;p=0.031)和色氨酸(AUC = 0.800;p=0.023)可确定严重肌少症的存在。

结论

血浆代谢组学分析表明,L-丙氨酸、葡萄糖酸、脯氨酸和色氨酸可能是严重肌少症的潜在生物标志物。所鉴定的代谢物可为严重肌少症的潜在病理生理学提供新的见解,并为预防干预提供依据。

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