Utilising novel technologies to predict muscle loss and muscle quality

A key hallmark of the natural biology of ageing is a progressive loss of skeletal muscle mass, strength and aerobic capacity, termed 'sarcopenia'. The association between muscle loss (mass and quality) and increased incidence of falls, fractures, metabolic disease and other health complications indicates that the burden of our ageing society on health-care systems will increase dramatically over the upcoming decades.

Whilst a degree of sarcopenia appears to be inevitable as we age, its rate of onset is highly modifiable based on environmental factors such as physical activity, nutrition, and inflammation (Wall et al, Ageing Res Rev. 2013;12). Indeed, physical inactivity/unloading has been proposed as a primary factor contributing to the functional decline in older individuals, particularly of the postural muscles of the lower limbs (thigh and calf), resulting in negative effects on gait, walking motor control, and walking economy. Importantly, lower walking economy after disuse can further contribute to the reduced daily activity in the older population (Floreani et al, PLoS One. 2018;13) resulting in a lower quality of life.

Mechanistic in vivo human studies investigating muscle loss with physical unloading have generally adopted limb immobilisation or prolonged bed rest models. Such studies have led to clear characterisations of muscle disuse atrophy of the lower limbs of older individuals, particularly the gastrocnemius (De Boer et al. Eur J Appl Physiol. 2008;104), and identified a reduction in skeletal muscle protein synthesis in response to nutrition ("anabolic resistance") as a primary mechanism. However, such studies have failed to identify fully effective countermeasures. For example, calf raise and leg press exercises 2-3 times per week had a minimal effect on the 50% decline in plantar flexion function, architecture (Reeves et al, J Gravit Physiol. 2002;9) and tendon stiffness (Reeves et al. J Appl Physiol. 2005;98), during 90 days bed rest. Moreover, while such models of physical unloading provide a controlled model for isolating disuse per se in humans, it ignores other key drivers of muscle atrophy inherent to ageing, such as inflammation and inadequate nutrition. This PhD will focus on the mechanisms, progression, and prevention of sarcopenia by addressing the following objectives:

1. Understand the causes of muscle atrophy using a unique 'ocean rowing' model system that integrates undernutrition, physical inactivity, and inflammation.
2. Improve interventions to mitigate muscle loss into old age, such as nutrition and exercise programmes.
3. Support rehabilitation by implementing these interventions through the development of predictive technologies using wearable devices and apps.
4. Ensure interventions are effective at improving healthcare by being intuitive, low cost and minimally intrusive.

The proposed research aligns with the UKRI Healthy Ageing Challenge and more specifically with the grand challenges of the EPSRC Developing Future Therapies; Frontiers of Physical Intervention, and Rehabilitation.