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August 24, 2021 03:30 am

Mathematical Model Predicts Best Way To Build Muscle

An anonymous reader quotes a report from Phys.Org: Researchers have developed a mathematical model that can predict the optimum exercise regime for building muscle. The researchers, from the University of Cambridge, used methods of theoretical biophysics to construct the model, which can tell how much a specific amount of exertion will cause a muscle to grow and how long it will take. The model could form the basis of a software product, where users could optimize their exercise regimes by entering a few details of their individual physiology. The results, reported in the Biophysical Journal, suggest that there is an optimal weight at which to do resistance training for each person and each muscle growth target. Muscles can only be near their maximal load for a very short time, and it is the load integrated over time which activates the cell signaling pathway that leads to synthesis of new muscle proteins. But below a certain value, the load is insufficient to cause much signaling, and exercise time would have to increase exponentially to compensate. The value of this critical load is likely to depend on the particular physiology of the individual. In 2018, the Cambridge researchers started a project on how the proteins in muscle filaments change under force. They found that main muscle constituents, actin and myosin, lack binding sites for signaling molecules, so it had to be the third-most abundant muscle component -- titin -- that was responsible for signaling the changes in applied force. Whenever part of a molecule is under tension for a sufficiently long time, it toggles into a different state, exposing a previously hidden region. If this region can then bind to a small molecule involved in cell signaling, it activates that molecule, generating a chemical signal chain. Titin is a giant protein, a large part of which is extended when a muscle is stretched, but a small part of the molecule is also under tension during muscle contraction. This part of titin contains the so-called titin kinase domain, which is the one that generates the chemical signal that affects muscle growth. The molecule will be more likely to open if it is under more force, or when kept under the same force for longer. Both conditions will increase the number of activated signaling molecules. These molecules then induce the synthesis of more messenger RNA, leading to production of new muscle proteins, and the cross-section of the muscle cell increases. This realization led to the current work. [The researchers] set out to constrict a mathematical model that could give quantitative predictions on muscle growth. They started with a simple model that kept track of titin molecules opening under force and starting the signaling cascade. They used microscopy data to determine the force-dependent probability that a titin kinase unit would open or close under force and activate a signaling molecule. They then made the model more complex by including additional information, such as metabolic energy exchange, as well as repetition length and recovery. The model was validated using past long-term studies on muscle hypertrophy. "Our model offers a physiological basis for the idea that muscle growth mainly occurs at 70% of the maximum load, which is the idea behind resistance training," said [one of the paper's authors]. "Below that, the opening rate of titin kinase drops precipitously and precludes mechanosensitive signaling from taking place. Above that, rapid exhaustion prevents a good outcome, which our model has quantitatively predicted." [...] The model also addresses the problem of muscle atrophy, which occurs during long periods of bed rest or for astronauts in microgravity, showing both how long can a muscle afford to remain inactive before starting to deteriorate, and what the optimal recovery regime could be.

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