̽��ֱ�� of Cambridge - muscle

Mathematical model predicts best way to build muscle

sc604 — Mon, 23 Aug 2021 04:28:37 +0000

̽��ֱ��researchers, from the ̽��ֱ�� 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. ̽��ֱ��model could form the basis of a software product, where users could optimise their exercise regimes by entering a few details of their individual physiology.

̽��ֱ��model is based on earlier work by the same team, which found that a component of muscle called titin is responsible for generating the chemical signals which affect muscle growth.

̽��ֱ��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 signalling pathway that leads to synthesis of new muscle proteins. But below a certain value, the load is insufficient to cause much signalling, and exercise time would have to increase exponentially to compensate. ̽��ֱ��value of this critical load is likely to depend on the particular physiology of the individual.

We all know that exercise builds muscle. Or do we? “Surprisingly, not very much is known about why or how exercise builds muscles: there’s a lot of anecdotal knowledge and acquired wisdom, but very little in the way of hard or proven data,” said Professor Eugene Terentjev from Cambridge’s Cavendish Laboratory, one of the paper’s authors.

When exercising, the higher the load, the more repetitions or the greater the frequency, then the greater the increase in muscle size. However, even when looking at the whole muscle, why or how much this happens isn’t known. ̽��ֱ��answers to both questions get even trickier as the focus goes down to a single muscle or its individual fibres.

Muscles are made up of individual filaments, which are only 2 micrometres long and less than a micrometre across, smaller than the size of the muscle cell. “Because of this, part of the explanation for muscle growth must be at the molecular scale,” said co-author Neil Ibata. “ ̽��ֱ��interactions between the main structural molecules in muscle were only pieced together around 50 years ago. How the smaller, accessory proteins fit into the picture is still not fully clear.”

This is because the data is very difficult to obtain: people differ greatly in their physiology and behaviour, making it almost impossible to conduct a controlled experiment on muscle size changes in a real person. “You can extract muscle cells and look at those individually, but that then ignores other problems like oxygen and glucose levels during exercise,” said Terentjev. “It’s very hard to look at it all together.”

Terentjev and his colleagues started looking at the mechanisms of mechanosensing – the ability of cells to sense mechanical cues in their environment – several years ago. ̽��ֱ��research was noticed by the English Institute of Sport, who were interested in whether it might relate to their observations in muscle rehabilitation. Together, they found that muscle hyper/atrophy was directly linked to the Cambridge work.

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 signalling molecules, so it had to be the third-most abundant muscle component – titin – that was responsible for signalling 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 signalling, 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.

̽��ֱ��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 signalling 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 realisation led to the current work, started by Ibata, himself a keen athlete. “I was excited to gain a better understanding of both the why and how of muscle growth,” he said. “So much time and resources could be saved in avoiding low-productivity exercise regimes, and maximising athletes’ potential with regular higher value sessions, given a specific volume that the athlete is capable of achieving.”

Terentjev and Ibata 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 signalling 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 signalling molecule.

They then made the model more complex by including additional information, such as metabolic energy exchange, as well as repetition length and recovery. ̽��ֱ��model was validated using past long-term studies on muscle hypertrophy.

“While there is experimental data showing similar muscle growth with loads as little as 30% of maximum load, our model suggests that loads of 70% are a more efficient method of stimulating growth,” said Terentjev, who is a Fellow of Queens' College. “Below that, the opening rate of titin kinase drops precipitously and precludes mechanosensitive signalling from taking place. Above that, rapid exhaustion prevents a good outcome, which our model has quantitatively predicted.”

“One of the challenges in preparing elite athletes is the common requirement for maximising adaptations while balancing associated trade-offs like energy costs,” said Fionn MacPartlin, Senior Strength & Conditioning Coach at the English Institute of Sport. “This work gives us more insight into the potential mechanisms of how muscles sense and respond to load, which can help us more specifically design interventions to meet these goals.”

̽��ֱ��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.

Eventually, the researchers hope to produce a user-friendly software-based application that could give individualised exercise regimes for specific goals. ̽��ֱ��researchers also hope to improve their model by extending their analysis with detailed data for both men and women, as many exercise studies are heavily biased towards male athletes.

Reference:
Neil Ibata and Eugene M. Terentjev. ‘Why exercise builds muscles: Titin mechanosensing controls skeletal muscle growth under load.’ Biophysical Journal (2021). DOI: 10.1016/j.bpj.2021.07.023

Researchers have developed a mathematical model that can predict the optimum exercise regime for building muscle.

Surprisingly, not very much is known about why or how exercise builds muscles: there’s a lot of anecdotal knowledge and acquired wisdom, but very little in the way of hard or proven data

Eugene Terentjev

John Arano on Unsplash

Woman lifting weights

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Common strength ‘genes’ identified for first time

cjb250 — Wed, 12 Jul 2017 09:28:41 +0000

̽��ֱ��researchers used data on hand grip strength from more than 140,000 participants in the UK Biobank study, combined with 50,000 additional individuals from the UK, Netherlands, Denmark and Australia, to identify sixteen common genetic variants that are associated with muscle strength.

Dan Wright, joint first author on this paper and a PhD student at the Medical Research Council Epidemiology (MRC) Unit at the ̽��ֱ�� of Cambridge, said: “ ̽��ֱ��very large number of individuals participating in UK Biobank provides a powerful resource for identifying genes involved in complex traits such as muscle strength, and helps us understand their underlying biology and its relevance to health.”

Many of these variants were located within or near to genes known to play a role in biological processes highly relevant to muscle function, including the structure and function of muscle fibres, and the communication of the nervous system with muscle cells.

Mutations in some of the genes highlighted are also known to be associated with severe monogenic syndromes – conditions caused by a single genetic mutations – characterised by compromised muscle function. This demonstrates that genetic variation in genes which cause serious muscular conditions may also influence differences in strength in the general population.

Dr Robert Scott, who co-led the study with colleagues from the MRC Epidemiology Unit, said: “While we have long suspected a role for genetics in the variation in muscle strength, these findings give the first insights into some of the specific genetic variants that underpin variation in strength.

“These could be important steps towards identifying new treatments to prevent or treat muscle weakness.”

Hand grip strength has been reported to be associated with many health outcomes, including risk of mortality, cardiovascular disease, and fracture – although it has been unclear whether variation in strength actually causes these outcomes, or simply reflects underlying disease processes.

Using the sixteen genetic variants identified for strength, the researchers were able to investigate the hypothesised causal link between strength and these adverse health outcomes. Their study found no evidence that lower strength causally increases risk of death or cardiovascular disease, but they did find evidence that higher muscular strength reduces risk of fracture, supporting the use of strength training interventions as a strategy to reduce risk of fractures.

Professor Nick Wareham, director of the MRC Epidemiology Unit and a senior author of the study, noted: “This work highlights the importance of muscle strength in the prevention of fractures and the complications which can often follow a fall.”

Reference
Willems, SM et al. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nature Communications; 12 July 2017; DOI: 10.1038/ncomms16015

Common genetic factors that influence muscle strength in humans have been identified for the first time in a study led by researchers from the ̽��ֱ�� of Cambridge and published today in Nature Communications.

̽��ֱ��very large number of individuals participating in UK Biobank provides a powerful resource for identifying genes involved in complex traits such as muscle strength

Dan Wright

Thomas Morris

Lose Weight and Gain Muscle

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Animals first flex their muscles

sc604 — Wed, 27 Aug 2014 07:15:00 +0000

An unusual new fossil discovery of one of the earliest animals on earth may also provide the oldest evidence of muscle tissue – the bundles of cells that make movement in animals possible.

̽��ֱ��fossil, dating from 560 million years ago, was discovered in Newfoundland, Canada. On the basis of its four-fold symmetry, morphological characteristics, and what appear to be some of the earliest impressions of muscular tissue, researchers from the ̽��ֱ�� of Cambridge, in collaboration with the ̽��ֱ�� of Oxford and the Memorial ̽��ֱ�� of Newfoundland, have interpreted it as a cnidarian: the group which contains modern animals such as corals, sea anemones and jellyfish. ̽��ֱ��results are published today (27 August) in the journal Proceedings of the Royal Society B.

Historically, the origin, evolution and spread of animals has been viewed as having begun during the Cambrian Explosion, a period of rapid evolutionary development starting 541 million years ago when most major animal groups first appear in the fossil record.

“However, in recent decades, discoveries of preserved trackways and chemical evidence in older rocks, as well as molecular comparisons, have indirectly suggested that animals may have a much earlier origin than previously thought,” said Dr Alex Liu of Cambridge’s Department of Earth Sciences, lead author of the paper.

“ ̽��ֱ��problem is that although animals are now widely expected to have been present before the Cambrian Explosion, very few of the fossils found in older rocks possess features that can be used to convincingly identify them as animals,” said Liu. “Instead, we study aspects of their ecology, feeding or reproduction, in order to understand what they might have been.”

̽��ֱ��new fossil, named Haootia quadriformis, dates from the Ediacaran Period, an interval spanning 635 to 541 million years ago. It differs from any previously described Ediacaran fossil, as it comprises of bundles of fibres in a broadly four-fold symmetrical arrangement: a body plan that is similar to that seen in modern cnidarians.

̽��ֱ��researchers determined that the similarities between Haootia quadriformis and both living and fossil cnidarians suggest that the organism was probably a cnidarian, and that the bundles represent muscular tissue. This would make it not only a rare example of an Ediacaran animal, but also one of the oldest fossils to show evidence of muscle anywhere in the world.

“ ̽��ֱ��evolution of muscular animals, in possession of muscle tissues that enabled them to precisely control their movements, paved the way for the exploration of a vast range of feeding strategies, environments, and ecological niches, allowing animals to become the dominant force in global ecosystems,” said Liu.

̽��ֱ��research was funded by the Natural Environment Research Council, the Natural Sciences and Engineering Research Council of Canada, the Burdett Coutts Fund of the ̽��ֱ�� of Oxford, and the National Geographic Global Exploration Fund Northern Europe.

Inset image: Artist reconstruction of Haootia quadriformis. Credit: Martin Brasier

A new fossil discovery identifies the earliest evidence for animals with muscles.

Animals may have a much earlier origin than previously thought

Alex Liu

Alex Liu/Jack Matthews

Fossil of Haootia quadriformis

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