Exercise 'prehabilitation': A novel intervention to protect against disuse-induced muscle atrophy and sarcopenia in the old

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Skeletal muscle mass plays an essential role in activities of daily living and regulation of metabolic health. Ageing is associated with a progressive decline in skeletal muscle mass (sarcopenia) that compromises tasks of daily living, metabolic health and increases the risk of falls, fractures and mortality. The healthcare costs associated with treating age-related musculoskeletal decline are vast, and continue to grow with our expanding ageing population. Of concern is that ~30% of those aged 75-84 years suffer from sarcopenia. Thus, interventions to reduce the progression of age-related muscle wasting will improve the quality of life in older individuals and have a profound impact on healthcare expenditure. To place this into context, a 10% reduction in the incidence of sarcopenia would result in an enormous reduction in healthcare expenditure associated with muscle deterioration (estimated annual cost to the NHS of £5.7 billion).Ageing is associated with an impairment in the normally healthy muscle metabolic response to nutrition, a phenomenon that has been termed 'anabolic resistance'. Age-related muscle anabolic resistance to nutrition may underpin the progression of sarcopenia. The root-cause of age-related muscle anabolic resistance is complex, but may be partly related to periods of disuse and inactivity, which occur with increasing frequency in older individuals. Specifically, the dysregulation in muscle metabolism that occurs during successive periods of short-term disuse and inactivity may accumulate over time to form the characteristic muscle anabolic resistance of ageing. Alarmingly, muscle deterioration occurs soon after the onset of disuse in older adults. This is important as the average length of hospital stay in older individuals is 5-6 days. Therefore, we believe a focus on maintaining healthy muscle metabolism during short-term disuse events is an important research priority in the fight against sarcopenia. Resistance exercise is a potent stimulus for muscle anabolism and can offset muscle loss during disuse in older individuals. However, older individuals are typically unable (or unwilling) to perform strenuous physical activities during disuse events. Interestingly, we recently observed that resistance exercise can restore the muscle anabolic response to nutrition in older individuals, and this enhanced metabolic response persists for several days after exercise completion (after older individuals have returned to a sedentary lifestyle). Therefore, resistance exercise prior to short-term disuse (termed 'prehabilitation') may protect muscle mass, strength and metabolic function in older individuals, with important implications for the progression sarcopenia and promotion of healthy ageing. In the proposed project, we will investigate whether resistance exercise prehabilitation protects against muscle and strength loss during short-term disuse in older individuals. A cohort of healthy older individuals will complete single-leg exercise prehabilitation (for comparison with the untrained control leg), consisting of either single or multiple bouts of resistance exercise. Immediately following exercise prehabilitation, participants will undergo 5 days of strict bed-rest. Detailed assessment of muscle size, architecture, and strength will conducted prior-to and following bed-rest. Furthermore, we will use sophisticated measurement techniques to understand the precise mechanisms that underpin alterations in muscle size and strength during short-term bed rest, and whether adaptations in these mechanisms can explain the protective effects of exercise prehabilitation on muscle health. Ultimately, we hope to demonstrate that exercise prehabilitation is an effective means of preventing muscle deterioration during short-term disuse in older individuals, which will ultimately slow the trajectory of sarcopenia and promote healthy, independent ageing in a diverse and expanding older population.