人体肌肉疏松症不同阶段的神经肌肉损伤。

IF 9.4 1区 医学 Q1 GERIATRICS & GERONTOLOGY
Fabio Sarto, Martino V. Franchi, Jamie S. McPhee, Daniel W. Stashuk, Matteo Paganini, Elena Monti, Maira Rossi, Giuseppe Sirago, Sandra Zampieri, Evgeniia S. Motanova, Giacomo Valli, Tatiana Moro, Antonio Paoli, Roberto Bottinelli, Maria A. Pellegrino, Giuseppe De Vito, Helen M. Blau, Marco V. Narici
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引用次数: 0

摘要

背景:运动神经元和神经肌肉接头(NMJ)的退化以及运动单位(MUs)的丧失导致了与肌肉疏松症相关的老年性肌肉萎缩和无力。然而,这些特征尚未在人体中得到全面研究。本研究旨在比较肌肉疏松症不同阶段的神经肌肉系统完整性和功能,尤其关注 NMJ 的稳定性和 MU 的特性:我们招募了 42 名年轻人(Y)(年龄为 25.98 ± 4.6 岁;57% 为女性)和 88 名老年人(年龄为 75.9 ± 4.7 岁;55% 为女性)。老年人组根据欧洲老年人肌肉疏松症工作组的修订指南2进行了肌肉疏松症筛查。在所有组别中,膝关节伸肌肌力通过等长测力计进行评估,肌肉形态通过超声波进行评估,肌肉电图(iEMG)通过肌内肌电图(MU)进行评估。此外,还采集了 MU 数量估计值(iMUNE)和血液样本。在 16 名 Y 岁和 52 名老年参与者的子组中收集了肌肉活组织切片:结果:39 名老年人为非肌肉疏松者(NS),31 名为前肌肉疏松者(PS),18 名为肌肉疏松者(S)。在不同的肌肉疏松期,股四头肌的力量、横截面积和韧带瘦肉含量都在逐渐减少(所有 P 均得出结论):MU特性的改变、轴突损伤、神经支配的改变以及NMJ的不稳定性是神经肌肉系统老化的显著特征。这些神经肌肉变化伴随着肌肉萎缩和虚弱;然而,它们似乎早于临床诊断的肌少症,因为在年长的 NS 患者身上已经可以检测到。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Neuromuscular impairment at different stages of human sarcopenia

Neuromuscular impairment at different stages of human sarcopenia

Background

Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age-related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties.

Methods

We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants.

Results

Thirty-nine older individuals were non-sarcopenic (NS), 31 pre-sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross-sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P < 0.0001). Handgrip force and the Short Physical Performance Battery score also showed a diminishing trend. iEMG analyses revealed elevated near fibre segment jitter in NS, PS and S compared with Y (Y vs. NS and S: P < 0.0001; Y vs. PS: P = 0.0169), suggestive of age-related impaired NMJ transmission. Increased C-terminal agrin fragment (P < 0.0001) and altered caveolin 3 protein expression were consistent with age-related NMJ instability in all the older groups. The iMUNE was lower in all older groups (P < 0.0001), confirming age-related loss of MUs. An age-related increase in MU potential complexity was also observed. These observations were accompanied by increased muscle denervation and axonal damage, evinced by the increase in neural cell adhesion molecule-positive fibres (Y vs. NS: P < 0.0001; Y vs. S: P = 0.02) and the increase in serum concentration of neurofilament light chain (P < 0.0001), respectively. Notably, most of these MU and NMJ parameters did not differ when comparing older individuals with or without sarcopenia.

Conclusions

Alterations in MU properties, axonal damage, an altered innervation profile and NMJ instability are prominent features of the ageing of the neuromuscular system. These neuromuscular alterations are accompanied by muscle wasting and weakness; however, they appear to precede clinically diagnosed sarcopenia, as they are already detectable in older NS individuals.

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来源期刊
Journal of Cachexia Sarcopenia and Muscle
Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-
CiteScore
13.30
自引率
12.40%
发文量
234
审稿时长
16 weeks
期刊介绍: The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.
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