From motor cortex to muscle: Novel interventions to address the discordant relationship between declines in muscle size and strength in older people

从运动皮层到肌肉：解决老年人肌肉大小和力量下降之间不一致关系的新干预措施

• 批准号: 2277953
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2277953
• 关键词: motor; cortex; muscle; Novel; interventions

Age-related loss of muscle strength is often explained by the concomitant reduction in muscle mass, however the former appears to decline more rapidly than the latter and this discordant relationship is poorly described, and often entirely overlooked. Alterations in neural mechanisms are a likely candidate here; work from our group has identified striking age-related differences in motor nerve/muscle recruitment strategies, including reduced firing frequency, diminished transmission stability at the neuromuscular junction (NMJ), and reduced heterogeneity of motor unit size during voluntary contractions in older adults. Thus, neural alterations must be considered. Whilst resistance exercise training (RET) improves the ability to recruit/activate muscle (so called 'neural drive'), it is not always feasible for older frail individuals to undergo strenuous exercise. Therefore, new interventions are required. Electrical stimulation (ES) targeting sensory and/or motor neurons has already been shown to increase the excitability of spinal circuits as well as motor neuron pools and this may result in increased recruitment of motor units when applied during exercise, subsequently enhancing exercise efficiency- however evidence for this is lacking. There is a critical need to address age-related alterations in motor pathways, from the motor cortex to muscle fibres, that negatively impact muscle strength and control, and to offer feasible, effective interventions for frail older individuals, especially those that offer potential translation to clinical settings. The proposed project will investigate age-related decrements in neural drive and neuromuscular function in humans, and will apply a number of appropriate interventions. The successful candidate will join a leading group in the field of musculoskeletal ageing, and will be trained in a range of techniques including intramuscular electromyography (iEMG), transcranial magnetic stimulation (TMS), immunohistochemistry and further techniques of molecular biology.

与年龄相关的肌肉力量丧失通常用肌肉质量的伴随减少来解释，然而前者似乎比后者下降得更快，而且这种不一致的关系很少被描述，而且常常被完全忽视。神经机制的改变可能是这里的一个候选者。我们小组的工作发现了运动神经/肌肉募集策略中与年龄相关的显着差异，包括放电频率降低、神经肌肉接头（NMJ）传输稳定性降低以及老年人随意收缩期间运动单位大小的异质性降低。因此，必须考虑神经改变。 虽然阻力运动训练 (RET) 可以提高募集/激活肌肉的能力（所谓的“神经驱动”），但对于年老体弱的人来说，进行剧烈运动并不总是可行的。 Therefore, new interventions are required.针对感觉和/或运动神经元的电刺激 (ES) 已被证明可以增加脊髓回路以及运动神经元池的兴奋性，这可能会导致运动过程中运动单位的募集增加，从而提高运动效率，但缺乏这方面的证据。 迫切需要解决从运动皮层到肌肉纤维的运动通路中与年龄相关的变化，这些变化会对肌肉力量和控制产生负面影响，并为体弱的老年人提供可行、有效的干预措施，特别是那些为临床环境提供潜在转化的干预措施。 拟议的项目将研究人类神经驱动和神经肌肉功能与年龄相关的衰退，并将采取一些适当的干预措施。成功的候选人将加入肌肉骨骼衰老领域的领先小组，并将接受一系列技术的培训，包括肌内肌电图（iEMG）、经颅磁刺激（TMS）、免疫组织化学和进一步的分子生物学技术。