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

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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.