He Nana, Zhang Yue Lin, Zhang Yue, Feng Beili, Zheng Zaixing, Wang Dongjuan, Zhang Shun, Guo Qi, Ye Honghua
Department of Experimental Medical Science, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.
Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China.
Front Genet. 2020 Mar 5;11:167. doi: 10.3389/fgene.2020.00167. eCollection 2020.
sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is a major cause of morbidity and mortality in elders. Current diagnostic criteria of sarcopenia have not been agreed internationally, and the clinical diagnostic biomarkers for sarcopenia have not been identified. Circulating miRNAs (miRNAs, miRs) have recently been characterized as novel biomarkers for sarcopenia. However, the change of circulating miRNAs in response to sarcopenia are still not fully understood. Here, we enrolled a total of 93 elderly patients clinically diagnosed with sarcopenia and matching 93 non-sarcopenia elderly in this study. Specifically, levels of candidate circulating miRNAs which were involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were detected in these two groups. In small-sample screening experiments, plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels were significantly down-regulated in sarcopenia compared to those who non-sarcopenia. In contrast, miR-1, mir-133a, miR-133b, miR-21, miR-146a, miR-126, miR-221, and miR-20a were not changed significantly. Subsequently, we expanded the sample size to further detection and verification, and found that plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels in the sarcopenia group were significantly reduced compared to the non-sarcoma group, which is consistent with the results of the small-sample screening experiment. In addition, we showed that ASM/Height2, handgrip strength, knee extension and 4-meter velocity in sarcopenia group were significantly lower than those in non-sarcopenia group. Here we correlated the decrease of miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 in sarcopenia group and non-sarcopenia group with diagnostic indexes of sarcopenia (ASM/Height2, Handgrip strength and 4-meter velocity) after adjusting sex. The results showed that miR-208b and miR-155 changes were significantly correlated with handgrip strength in woman, miR-208b, miR-499, and miR-222 changes were significantly correlated with ASM/Height2 in man, while other miRNAs changes did not show a strong correlation with these diagnostic indexes. In conclusion, plasma miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 decrease in response to sarcopenia in the elderly. Although further studies are needed to clarify the potential use of circulating miRNAs as biomarkers of sarcopenia, present findings set the stage for defining circulating miRNAs as biomarkers and suggesting their physiological roles in elderly with sarcopenia.
肌肉减少症被定义为与衰老相关的疾病，其特征是骨骼肌质量、力量和功能下降，这是老年人发病和死亡的主要原因。目前，肌肉减少症的诊断标准尚未在国际上达成共识，且尚未确定肌肉减少症的临床诊断生物标志物。循环微RNA（miRNA，miRs）最近被鉴定为肌肉减少症的新型生物标志物。然而，循环miRNA对肌肉减少症的反应变化仍未完全了解。在本研究中，我们共纳入了93例临床诊断为肌肉减少症的老年患者，并匹配了93例非肌肉减少症老年人。具体而言，在这两组中检测了参与血管生成、炎症且在肌肉和/或心脏组织中富集的候选循环miRNA水平。在小样本筛选实验中，与非肌肉减少症患者相比，肌肉减少症患者血浆中miR-155、miR-208b、miR-222、miR-210、miR-328和miR-499水平显著下调。相比之下，miR-1、mir-133a、miR-133b、miR-21、miR-146a、miR-126、miR-221和miR-20a无显著变化。随后，我们扩大样本量进行进一步检测和验证，发现肌肉减少症组血浆中miR-155、miR-208b、miR-222、miR-210、miR-328和miR-499水平显著低于非肌肉减少症组，这与小样本筛选实验结果一致。此外，我们发现肌肉减少症组的四肢骨骼肌质量/身高²、握力、膝关节伸展和4米步行速度显著低于非肌肉减少症组。在此，我们在调整性别后，将肌肉减少症组和非肌肉减少症组中miR-208b、miR-499、miR-155、miR-222、miR-328和miR-210的降低与肌肉减少症的诊断指标（四肢骨骼肌质量/身高²、握力和4米步行速度）进行关联。结果显示，miR-208b和miR-155的变化与女性握力显著相关，miR-208b、miR-499和miR-222的变化与男性四肢骨骼肌质量/身高²显著相关，而其他miRNA变化与这些诊断指标无强相关性。总之，老年人肌肉减少症会导致血浆中miR-208b、miR-499、miR-155、miR-222、miR-328和miR-210降低。尽管需要进一步研究以阐明循环miRNA作为肌肉减少症生物标志物的潜在用途，但目前的研究结果为将循环miRNA定义为生物标志物并揭示其在肌肉减少症老年人中的生理作用奠定了基础。
