̽��ֱ�� of Cambridge - physiology

It’s all in the wrist: energy-efficient robot hand learns how not to drop the ball

sc604 — Wed, 12 Apr 2023 03:23:34 +0000

Researchers have designed a low-cost, energy-efficient robotic hand that can grasp a range of objects – and not drop them – using just the movement of its wrist and the feeling in its ‘skin’.

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

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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'Selfish brain' wins out when competing with muscle power, study finds

fpjl2 — Fri, 20 Oct 2017 11:51:43 +0000

Human brains are expensive – metabolically speaking. It takes lot of energy to run our sophisticated grey matter, and that comes at an evolutionary cost.

Now, a new investigation into the immediate trade-off that occurs inside us when we have to think fast and work hard at the same time is the first to demonstrate that – while both are impaired – our mental ability is less affected than our physical capacity.

Researchers say that the findings suggest a "preferential allocation of glucose to the brain", which they argue is likely to be an evolved trait – as prioritising quick thinking over fast moving, for example, may have helped our species survive and thrive.

Scientists from the ̽��ֱ�� of Cambridge's PAVE (Phenotypic Adaptability, Variation and Evolution) research group tested 62 male students drawn from the ̽��ֱ��'s elite rowing crews. ̽��ֱ��participants had an average age of 21.

̽��ֱ��rowers performed two separate tasks: one memory, a three minute word recall test, and one physical, a three minute power test on a rowing machine.

They then performed both tasks at once, with individual scores compared to those from previous tests. As expected, the challenge of rowing and remembering at the same time reduced both physical and mental performance.

However, the research team found that change in recall was significantly less than the change in power output.

During the simultaneous challenge, recall fell by an average of 9.7%, while power fell by an average of 12.6%. Across all participants the drop in physical power was on average 29.8% greater than drop in cognitive function.

̽��ֱ��team say the results of their new study, published today in the journal Scientific Reports, add evidence to the 'selfish brain' hypothesis: that the brain has evolved to prioritise its own energy needs over those of peripheral organs, such as skeletal muscle.

"A well-fuelled brain may have offered us better survival odds than well-fuelled muscles when facing an environmental challenge," said Dr Danny Longman, the study's lead author from the PAVE team in Cambridge's Department of Archaeology.

" ̽��ֱ��development of an enlarged and elaborated brain is considered a defining characteristic of human evolution, but one that has come as a result of trade-offs.

"At the evolutionary level, our brains have arguably cost us decreased investment in muscle as well as a shrunken digestive system.

"Developmentally, human babies have more stored fat than other mammals, acting as an energy buffer that feeds our high cerebral requirements.

"On an acute level, we have now demonstrated that when humans simultaneously experience extremes of physical and mental exertion, our internal trade-off preserves cognitive function as the body's priority."

̽��ֱ��adult brain derives its energy almost exclusively from the metabolism of glucose. Yet skeletal muscle mass is also energetically expensive tissue, accounting for 20% of the human male 'basal metabolic rate' – the energy used when doing nothing.

Longman says a limited supply of blood glucose and oxygen means that, when active, skeletal muscle becomes a "powerful competitor" to the brain. "This is the potential mechanism for the fast-acting trade-off in brain and muscle function we see in just a three minute window."

"Trade-offs between organs and tissues allow many organisms to endure conditions of energy deficit through internal prioritising. However, this comes at a cost," said Longman.

He points to examples of this trade-off benefiting the brain in humans. " ̽��ֱ��selfish nature of the brain has been observed in the unique preservation of brain mass as bodies waste away in people suffering from long-term malnutrition or starvation, as well as in children born with growth restriction."

New research on our internal trade-off when physical and mental performance are put in direct competition has found that cognition takes less of a hit, suggesting more energy is diverted to the brain than body muscle. Researchers say the findings support the ‘selfish brain’ theory of human evolution.

A well-fuelled brain may have offered us better survival odds than well-fuelled muscles when facing an environmental challenge

Danny Longman

Lead researcher Dr Danny Longman rowing with the Cambridge ̽��ֱ�� Boat Club. This is an example of the type and standard of the sample population used in the study.

̽��ֱ��study

Protocol A – isolated power test:
Participants rowed at maximal effort for 3 minutes, and their average Wattage was recorded.

Protocol B – isolated recall test:
Participants performed a free recall word task in which they were shown 75 words from the Toronto Word Pool for a 3 minute period. They then had 5 minutes to recall and write as many words as possible. ̽��ֱ��number of words correctly recalled during a given time period was recorded.

Protocol C – combined 'trade-off' test:
Participants did both (but with a different word set), and their average Wattage and number of words correctly recalled was recorded. Researchers used 'paired samples t-tests' to compare power output between Protocols A and C, and for comparing free recall in Protocols B and C. They then compared the two differences, and found that the percentage change in free recall was significantly less than the percentage change in power output – an average of 29.8%.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Himalayan powerhouses: how Sherpas have evolved superhuman energy efficiency

cjb250 — Mon, 22 May 2017 19:00:54 +0000

̽��ֱ��findings could help scientists develop new ways of treating hypoxia – lack of oxygen – in patients. A significant proportion of patients in intensive care units (ICUs) experience potentially life-threatening hypoxia, a complication associated with conditions from haemorrhage to sepsis.

When oxygen is scarce, the body is forced to work harder to ensure that the brain and muscles receive enough of this essential nutrient. One of the most commonly observed ways the body has of compensating for a lack of oxygen is to produce more red blood cells, which are responsible for carrying oxygen around the body to our organs. This makes the blood thicker, however, so it flows more slowly and is more likely to clog up blood vessels.

Mountain climbers are often exposed to low levels of oxygen, particularly at high altitudes. This is why they often have to take time during long ascents to acclimatise to their surroundings, giving the body enough time to adapt itself and prevent altitude sickness. In addition, they may take oxygen supplies to supplement the thin air.

Scientists have known for some time that people have different responses to high altitudes. While most climbers require additional oxygen to scale Mount Everest, whose peak is 8,848m above sea level, a handful of climbers have managed to do so without. Most notably, Sherpas, an ethnic group from the mountain regions of Nepal, are able to live at high altitude with no apparent consequences to their health – as a result, many act as guides to support expeditions in the Himalayas, and two Sherpas are known to have reached the summit of Everest an incredible 21 times.

Previous studies have suggested differences between Sherpas and people living in non-high altitude areas, known collectively as ‘lowlanders’, including fewer red blood cells in Sherpas at altitude, but higher levels of nitric oxide, a chemical that opens up blood vessels and keeps blood flowing.

Evidence suggests that the first humans were present on the Tibetan Plateau around 30,000 years ago, with the first permanent settlers appearing between 6,000-9,000 years ago. This raises the possibility that they have evolved to adapt to the extreme environment. This is supported by recent DNA studies, which have found clear genetic differences between Sherpa and Tibetan populations on the one hand and lowlanders on the other. Some of these differences were in their mitochondrial DNA – the genetic code that programmes mitochondria, the body’s ‘batteries’ that generate our energy.

To understand the metabolic differences between the Sherpas and lowlanders, a team of researchers led by scientists at the ̽��ֱ�� of Cambridge followed two groups as they made a gradual ascent up to Everest Base Camp at an elevation of 5,300m. ̽��ֱ��expedition, Xtreme Everest 2, was led by Dr Daniel Martin from ̽��ֱ�� College London.

Xtreme Everest is a project that aims to improve outcomes for people who become critically ill by understanding how our bodies respond to the extreme altitude on the world’s highest mountain. This year marks 10 years since the group’s first expedition to Everest.

̽��ֱ��lowlanders group comprised 10 investigators selected to operate the Everest Base Camp laboratory, where the mitochondrial studies were carried out by James Horscroft and Aleks Kotwica, two PhD students at the ̽��ֱ�� of Cambridge. They took samples, including blood and muscle biopsies, in London to give a baseline measurement, then again when they first arrived at Base Camp and a third time after two months at Base Camp. These samples were compared with those taken from 15 Sherpas, all of whom were living in relatively low-lying areas, rather than being the ‘elite’ high altitude climbers. ̽��ֱ��Sherpas’ baseline measurements were taken at Kathmandu, Nepal.

̽��ֱ��researchers found that even at baseline, the Sherpas’ mitochondria were more efficient at using oxygen to produce ATP, the energy that powers our bodies.

As predicted from genetic differences, they also found lower levels of fat oxidation in the Sherpas. Muscles have two ways to get energy – from sugars, such as glucose, or from burning fat (fat oxidation). ̽��ֱ��majority of the time we get our energy from the latter source; however, this is inefficient, so at times of physical stress, such as when exercising, we take our energy from sugars. ̽��ֱ��low levels of fat oxidation again suggest that the Sherpas are more efficient at generating energy.

̽��ֱ��measurements taken at altitude rarely changed from the baseline measurement in the Sherpas, suggesting that they were born with such differences. However, for lowlanders, measurements tended to change after time spent at altitude, suggesting that their bodies were acclimatising and beginning to mimic the Sherpas’ bodies.

One of the key differences, however, was in phosphocreatine levels. Phosphocreatine is an energy reserve that acts as a buffer to help muscles contract when no ATP is present. In lowlanders, after two months at high altitude, phosphocreatine levels crash, whereas in Sherpas levels actually increase.

In addition, the team found that while levels of free radicals increase rapidly at high altitude, at least initially, levels in Sherpas are very low. Free radicals are molecules created by a lack of oxygen that can be potentially damaging to cells and tissue.

“Sherpas have spent thousands of years living at high altitudes, so it should be unsurprising that they have adapted to become more efficient at using oxygen and generating energy,” says Dr Andrew Murray from the ̽��ֱ�� of Cambridge, the study’s senior author. “When those of us from lower-lying countries spend time at high altitude, our bodies adapt to some extent to become more ‘Sherpa-like’, but we are no match for their efficiency.”

̽��ֱ��team say the findings could provide valuable insights to explain why some people suffering from hypoxia fare much worse in emergency situations that others.

“Although lack of oxygen might be viewed as an occupational hazard for mountain climbers, for people in intensive care units it can be life threatening,” explains Professor Mike Grocott, Chair of Xtreme Everest from the ̽��ֱ�� of Southampton. “One in five people admitted to intensive care in the UK each year die and even those that survive might never regain their previous quality of life.

“By understanding how Sherpas are able to survive with low levels of oxygen, we can get clues to help us identify those at greatest risk in ICUs and inform the development of better treatments to help in their recovery.”

Dr Martin adds: “These findings are an important step forward for our translational research programme. They provide us with an insight as to how Shepras have adapted to low oxygen levels over countless generations. This new piece of the jigsaw will hopefully lead us towards finding new treatments that will benefit patients in intensive care.”

̽��ֱ��research was part-funded by the British Heart Foundation.

Reference
Horscroft, J et al. Metabolic basis to Sherpa altitude adaptation. PNAS; 22 May 2017; DOI: 10.1073/pnas.1700527114

Sherpas have evolved to become superhuman mountain climbers, extremely efficient at producing the energy to power their bodies even when oxygen is scarce, suggests new research published in the Proceedings of National Academy of Sciences (PNAS).

Sherpas have spent thousands of years living at high altitudes, so it should be unsurprising that they have adapted to become more efficient at using oxygen and generating energy

Andrew Murray

How Sherpas have evolved ‘superhuman’ energy efficiency

Niklassletteland

Sherpas on the Trail Nearing Lobuche, Nepal

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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