Shin Hyung Eun, Won Chang Won, Duque Gustavo, Kim Miji
Department of Health Sciences and Technology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Elderly Frailty Research Center, Department of Family Medicine, College of Medicine, Kyung Hee University, Kyung Hee University Medical Center, Seoul, Republic of Korea.
J Cachexia Sarcopenia Muscle. 2025 Aug;16(4):e70026. doi: 10.1002/jcsm.70026.
Low muscle strength, a key component of sarcopenia, is significant in the development of adverse health outcomes among older adults. MicroRNAs (miRNAs) have been implicated in mechanisms of sarcopenia; however, their specific functions in sarcopenia components, particularly low muscle strength, remain unclear. We aimed to examine distinct miRNA signatures associated with muscle mass, strength, and performance and to explore independent biomarkers for identifying older adults with low muscle strength.
Ninety-six older adults were selected from the Korean Frailty and Aging Cohort Study using stratified random sampling based on age and sex, and classified into four groups according to Asian Working Group for Sarcopenia 2019 criteria: normal (n = 25), low muscle mass (Low MM)-only (n = 23), low muscle strength (Low MS)-only (n = 25) and low physical performance (Low PP)-only (n = 23). MiRNA profiles were generated through miRNA sequencing, and differentially expressed (DE) miRNAs among groups were identified using log2|Fold Change (FC)| ≥ 1 and a Benjamini-Hochberg (BH)-adjusted p < 0.05. Subsequently, candidate miRNAs were validated by quantitative real-time polymerase chain reaction. Differences in relative miRNA expression between groups were assessed using analysis of variance. The utility of identified miRNAs for discriminating older adults with low muscle strength was assessed using receiver operating characteristic (ROC) analysis.
In 96 older adults (50.0% women, mean age 76.6 ± 3.6 years), 16, 5 and 1 DE miRNAs were observed in comparisons of Low MS-only vs. Low MM-only, Low PP-only vs. Low MM-only, and Low PP-only vs. Low MS-only, respectively (log2|FC| ≥ 1 and BH-adjusted p < 0.05). Among these, miR-144-3p, miR-142-3p and miR-122-3p overlapped across at least two comparisons. In the validation phase, miR-144-3p exhibited significantly higher expression in the Low MS-only group than in other groups. Areas under the ROC curve (AUC) for miR-144-3p were 0.943 (95% CI = 0.854-1.000), 0.836 (95% CI = 0.698-0.974) and 0.844 (95% CI = 0.700-0.989) for distinguishing the Low MS-only group from normal, Low MM-only and Low PP-only groups, respectively (p < 0.001). Kyoto Encyclopedia of Genes and Genomes analysis revealed that identified novel miRNAs were mainly associated with FoxO and insulin signalling (BH-adjusted p < 0.001), with a trend toward neurotrophic signalling (BH-adjusted p = 0.0647).
miR-144-3p was identified as a novel biomarker for low muscle strength among older adults, independent of muscle mass and physical performance. Longitudinal studies are required to determine whether the identified miRNAs can function as predictive biomarkers for muscle strength decline.
肌肉力量低下是肌少症的关键组成部分，在老年人不良健康结局的发生发展中具有重要意义。微小RNA（miRNA）与肌少症的发病机制有关；然而，它们在肌少症各组成部分，尤其是肌肉力量低下方面的具体功能仍不清楚。我们旨在研究与肌肉质量、力量和功能相关的独特miRNA特征，并探索用于识别肌肉力量低下老年人的独立生物标志物。
从韩国衰弱与老龄化队列研究中，根据年龄和性别采用分层随机抽样选取96名老年人，并根据2019年亚洲肌少症工作组标准分为四组：正常组（n = 25）、仅低肌肉量（Low MM）组（n = 23）、仅低肌肉力量（Low MS）组（n = 25）和仅低身体功能（Low PP）组（n = 23）。通过miRNA测序生成miRNA图谱，并使用log2|倍数变化（FC）|≥1和经Benjamini-Hochberg（BH）校正的p<0.05来鉴定组间差异表达（DE）的miRNA。随后，通过定量实时聚合酶链反应验证候选miRNA。使用方差分析评估组间相对miRNA表达的差异。使用受试者工作特征（ROC）分析评估所鉴定的miRNA区分肌肉力量低下老年人的效用。
在96名老年人（50.0%为女性，平均年龄76.6±3.6岁）中，仅Low MS组与仅Low MM组、仅Low PP组与仅Low MM组、仅Low PP组与仅Low MS组的比较中分别观察到16、5和1个DE miRNA（log2|FC|≥1且BH校正p<0.05）。其中，miR-144-3p、miR-142-3p和miR-122-3p在至少两次比较中重叠。在验证阶段，miR-144-3p在仅Low MS组中的表达明显高于其他组。miR-144-3p区分仅Low MS组与正常组、仅Low MM组和仅Low PP组的ROC曲线下面积（AUC）分别为0.943（95%CI = 0.854 - 1.000）、0.836（95%CI = 0.698 - 0.974）和0.844（95%CI = 0.700 - 0.989）（p<0.001）。京都基因与基因组百科全书分析显示，所鉴定的新型miRNA主要与FoxO和胰岛素信号通路相关（BH校正p<0.001），并有向神经营养信号通路发展的趋势（BH校正p = 0.0647）。
miR-144-3p被确定为老年人肌肉力量低下的一种新型生物标志物，独立于肌肉质量和身体功能。需要进行纵向研究以确定所鉴定的miRNA是否可作为肌肉力量下降的预测生物标志物。
