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About the project
Clinically relevant muscle loss and weakness, known as sarcopenia, affects 1 in 4 individuals aged over 80 years. Periods of forced disuse, for example after surgery, lead to sharp decreases in muscle function that are equivalent to years of regular ageing, and are linked to reduced neuromuscular junction (NMJ) integrity. Importantly, recovery from disuse is impaired in elderly individuals, accelerating the development of sarcopenia.

Since exercise improves NMJ stability, a potential solution is to perform exercise prior to disuse, known as prehabilitative exercise. The purpose of the proposed study is to uncover the mechanisms behind the impaired recovery in the elderly and the protective effects of prehabilitation. In this randomized controlled trial, young and elderly males and females will undergo prehabilitative exercise training for 4 weeks prior to 2 weeks of limb immobilization and 4 weeks of recovery. Muscle tissue biopsies will be collected for molecular analyses to investigate the impact of training and disuse on muscle denervation, and the muscle transcriptome and proteome at the single cell level.

A key method is the co-culture of motor neurons and muscle cells to identify the negative and positive factors for neurons, produced by inactive and exercised muscles, respectively. This study advances the sarcopenia research field by combining an important clinical question with state-of-the art methods and can alter clinical practice where patients are treated electively.