Data Sheet 1_Circulatory titin and miR-451a are possible sarcopenia biomarkers in elderly people.pdf

IntroductionSarcopenia is a clinical syndrome characterized by decline of muscle mass, strength or physical performance that occur with advancing age. Diagnosis is currently based on assessment of muscle mass and performance. New biomarkers are needed in clinical practice for diagnosis, monitoring and treatment of sarcopenia. The measurement in urine of titin (TTN), a muscular protein essential for structure and function of sarcomere, has been recently suggested as useful biomarker for the diagnosis of sarcopenia. The titin N-terminal fragment (N-TTN), produced by proteolysis during muscle damage, is released in the bloodstream and is secreted in the urine, and it was suggested as indicator of muscle injury. The primary aim of our study is to evaluate the potential of serum TTN and N-TTN expression as biomarker of sarcopenia, an aspect that has not been the subject of much research so far. Additionally, the secondary aim is to explore possible relationship between the serum expression of titin and miR-451a, its possible miRNA regulator.
MethodsWe verified serum TTN, N-TTN and miR-451a concentration in a cohort of 70 sarcopenic patients who were undergoing rehabilitation; results were compared to those obtained in 90 age- and sex-matched healthy controls (HC).
ResultsResults showed that TTN and N-terminal TTN (N-TTN) (p < 0.0005 for both) and miR-451a (p < 0.0001) were significantly upregulated in serum of patients compared to HC. Rehabilitation significantly reduced TTN and N-TTN expression (p < 0.05 for all), while induced a significant increase in miR-451a expression (p = 0.008); ROC analysis showed that the change of miR-451a may be a predictive biomarker for rehabilitation outcome (p = 0.0198).
DiscussionThis study suggests the involvement of TTN, N-TTN and miR-451a in sarcopenia; moreover, the monitoring of miR-451a concentration may be useful proxy to measure the effectiveness of rehabilitation intervention.

引言
肌肉减少症（Sarcopenia）是一种以随年龄增长出现的肌肉质量、力量或躯体运动能力下降为特征的临床综合征。目前其诊断主要基于肌肉质量与运动能力的评估。临床实践中亟需新型生物标志物用于肌肉减少症的诊断、病情监测与治疗。近期有研究提出，检测尿液中的肌联蛋白（titin, TTN）——一种对肌节（sarcomere）结构与功能至关重要的肌肉蛋白——可作为肌肉减少症的潜在诊断生物标志物。肌联蛋白N端片段（N-TTN）由肌肉损伤过程中的蛋白水解作用产生，释放入血并分泌至尿液中，曾被建议作为肌肉损伤的指示物。本研究的首要目的是评估血清TTN与N-TTN表达作为肌肉减少症生物标志物的潜力，这一方向目前尚未得到充分研究。此外，本研究的次要目的是探讨血清肌联蛋白表达与其潜在的微小RNA调控因子miR-451a之间的潜在关联。
方法
我们纳入70例正在接受康复治疗的肌肉减少症患者队列，检测其血清TTN、N-TTN与miR-451a浓度，并与90例年龄、性别匹配的健康对照（healthy controls, HC）的检测结果进行对比。
结果
结果显示，与健康对照相比，患者血清中的TTN、N端TTN（N-TTN，二者均p<0.0005）以及miR-451a（p<0.0001）均显著上调。康复治疗可显著降低TTN与N-TTN的表达水平（所有指标p<0.05），同时显著上调miR-451a的表达（p=0.008）；受试者工作特征（Receiver Operating Characteristic, ROC）分析显示，miR-451a的水平变化可作为康复治疗效果的预测生物标志物（p=0.0198）。
讨论
本研究表明TTN、N-TTN与miR-451a参与了肌肉减少症的发生发展；此外，监测血清miR-451a浓度可作为评估康复治疗有效性的有效替代指标。