C-terminal Agrin Fragment as a potential marker for sarcopenia caused by degeneration of the neuromuscular junction
C-terminal Agrin Fragment as a potential marker for sarcopenia caused by degeneration of the neuromuscular junction
复制标题
DOI：
10.1016/j.exger.2012.05.021
复制
发表时间：
2013-01-01
影响因子：
3.9
通讯作者：
Vrijbloed, J. W.
中科院分区：
文献类型：
--
作者：
Drey, M.;Sieber, C. C.;Vrijbloed, J. W.
简介：肌肉减少症被认为对受影响的个人和整个社会来说都是一个巨大的负担。已经讨论了这种老年综合征的多因素病因。在其他病理机制中，神经肌肉接头（NMJ）的退化可能具有重要意义。促突触剂集聚蛋白和抗突触剂神经胰蛋白酶之间的完整平衡确保了结构和功能完整的 NMJ。神经胰蛋白酶将天然运动神经元衍生的集聚蛋白过度裂解为 C 末端集聚蛋白片段 (CAF)，导致 NMJ 功能瓦解，并可能连续引起肌少症。本研究评估了以下假设：CAF 血清浓度是老年人四肢瘦体重损失的潜在标志。它还探讨了 CAF 浓度如何受到维生素 D 补充剂和体育锻炼的影响。方法：从参与培训干预研究的 69 名（47 名女性）社区居住的体弱老年人中采集血清，使用蛋白质印迹技术测量 CAF 浓度。在训练干预期开始之前，所有参与者都口服补充维生素 D3。通过双能 X 射线吸收测定法评估阑尾瘦体重 (aLM)。使用多元线性回归模型来确定与 CAF 浓度显着相关的因素。结果：四肢去脂质量、年龄和性别被确定为 CAF 浓度的显着解释因素。步态速度和握力与 CAF 浓度无关。男性参与者在 CAF 血清浓度和 aLM 之间表现出很强的相关性 (r=-0.524)，而女性参与者的情况并非如此 (r=-0.219)。维生素 D 补充和体育锻炼与 CAF 浓度降低显着相关，特别是对于最初 CAF 浓度较高的参与者。结论：C 末端 Agrin 片段可能是未来在受影响个体亚组中识别肌少症的潜在标志物。男性的肌肉质量下降似乎是与 CAF 相关的过程，而女性的情况可能更为复杂且涉及多个因素。补充维生素 D 和体育锻炼会降低 CAF 浓度，因此表明对 NMJ 具有潜在的积极作用。除了肌肉活检和肌电图检查之外，还计划对肌肉减少症患者进行进一步的前瞻性研究，以验证 CAF 概念的外部有效性。 (C) 2012 Elsevier Inc. 保留所有权利。
Introduction: Sarcopenia is considered to be an enormous burden for both the individuals affected and for society at large. A multifactorial aetiology of this geriatric syndrome has been discussed. Amongst other pathomechanisms, the degeneration of the neuromuscular junction (NMJ) may be of major relevance. The intact balance between the pro-synaptic agent agrin and the anti-synaptic agent neurotrypsin ensures a structurally and functionally intact NMJ. Excessive cleavage of the native motoneuron-derived agrin by neurotrypsin into a C-terminal Agrin Fragment (CAF) leads to functional disintegration at the NMJ and may consecutively cause sarcopenia. The present study evaluates the hypothesis that CAF serum concentration is a potential marker for the loss of appendicular lean mass in older adults. It also explores how CAF concentration is influenced by vitamin D supplementation and physical exercise.Method: Serum was taken from 69 (47 female) prefrail community-dwelling older adults participating in a training intervention study to measure the CAF concentration using the Western blot technique. All participants were supplemented orally with vitamin D3 before the training intervention period commenced. Appendicular lean mass (aLM) was evaluated by dual energy X-ray absorptiometry. Multiple linear regression models were used to identify factors significantly associated with CAF concentration.Results: Appendicular lean mass, age and sex were identified as significant explanatory factors for CAF concentration. Gait speed and hand grip strength were not associated with CAF concentration. Male participants showed a strong correlation (r=-0.524) between CAF serum concentration and aLM, whereas this was not the case (r=-0.219) in females. Vitamin D supplementation and physical exercise were significantly associated with a reduction in CAF concentration, especially in participants with initially high CAF concentrations.Conclusions: C-terminal Agrin Fragment could be a potential marker for identifying sarcopenia in a subgroup of affected individuals in the future. The decline of muscle mass seems to be a CAF-associated process in males, whereas the situation in females may be more complex and multifactorial. CAF concentration is reduced by vitamin D supplementation and physical exercise and therefore suggests a potentially positive effect on NMJs. Further prospective studies of sarcopenic patients in addition to muscle biopsy and electromyographical investigations are planned to verify the external validity of the CAF concept. (C) 2012 Elsevier Inc. All rights reserved.