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

肌肉力量的下降通常被解释为肌肉质量的减少，但前者似乎比后者下降得更快，这种不协调的关系描述得很差，往往被完全忽视。神经机制的改变是一个可能的候选人;我们小组的工作已经确定了运动神经/肌肉招募策略中与年龄相关的显著差异，包括放电频率降低，神经肌肉接头（NMJ）的传递稳定性降低，以及老年人自主收缩期间运动单位大小的异质性降低。因此，必须考虑神经系统的变化。 虽然阻力运动训练（RET）提高了招募/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。因此，需要采取新的干预措施。针对感觉和/或运动神经元的电刺激（ES）已经显示出增加脊髓回路以及运动神经元池的兴奋性，并且当在运动期间应用时，这可能导致运动单位的募集增加，随后提高运动效率-然而缺乏证据。 目前迫切需要解决与年龄相关的运动通路改变，从运动皮层到肌肉纤维，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，特别是那些可能转化为临床环境的干预措施。 拟议的项目将调查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导小组，并将接受一系列技术培训，包括肌内肌电图（iEMG），经颅磁刺激（TMS），免疫组织化学和分子生物学的进一步技术。

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.