Scientists at Liverpool John Moores University (LJMU) and the Australian Catholic University in Melbourne have established a new technique for studying muscle growth in humans that could rapidly advance treatments to prevent frailty in old age.
The findings published in FASEB J measure muscle responses at a finer level of detail and so could lead to better training methods, nutritional strategies or medicines that can be used to promote muscle growth (to enhance exercise performance) or prevent muscle wasting, which is an important contributor to frailty in old age.
The technique, termed Dynamic Proteome Profiling, provides comprehensive coverage of the early changes that occur within human muscle in response to exercise training. This was the first data on the rate at which new muscle proteins are made when volunteers performed strength training exercises.
Professor Jatin Burniston who is based at the LJMU School of Sport and Exercise Sciences explains: “Muscle is composed of thousands of different proteins and each protein makes a specific contribution to muscle function, for example some proteins are responsible for movement while others are required to provide energy.
“The proteins in muscle have a pretty tough time and often become damaged, but in healthy cells a sophisticated recycling system keeps protein quality high by continually breaking down and remaking each protein. When muscle fibres grow in response to weight training the amount of specific proteins is increased, and this is why muscle becomes larger and stronger.
“Until now, we have not been able to identify exactly which proteins are most responsive to exercise and whether that response is due to more of the protein being made or less of the protein being degraded/ broken down by the cell’s recycling machinery.”
Co-author Professor John Hawley, who is based at the Australian Catholic University in Melbourne adds: “The new level of measurement afforded by the novel technique means we can detect changes that would be missed by the previous method which measured the average response of all proteins in a muscle. Often, just a subset of proteins respond to any particular type of growth stimulus, and usually some proteins respond positively while at the same time others respond negatively so on average it could look as if there had been no change”.
How it works
During the course of an exercise training programme volunteers drink deuterium oxide (heavy water) and the deuterium labels every new protein that is made. The addition of deuterium to a protein alters its mass but it does not affect the function of the protein, so this technique is safe for use in humans.
Proteins are extracted from muscle biopsy samples and mass spectrometry is used to measure the amount of deuterium in each protein. The mass spectrometry data is also used to identify each protein and estimate its abundance. The abundance of each protein is determined by the balance between its synthesis rate and degradation rate, therefore, if the abundance of a protein changes and its rate of synthesis is known then its rate of degradation can be calculated.
The ability to identify muscle proteins and measure whether the amount of a protein has increased or decreased due to a change in either synthesis or degradation has widespread potential in health research. Ageing is associated with a loss of protein quality control that leads to an accumulation of damaged proteins which can become toxic to the cell. In muscle, this process of proteotoxicity could be responsible for the gradual loss of muscle mass and function seen in older adults. The Dynamic Proteome Profiling technique will help scientists to design lifestyle interventions or develop medicines that can specifically target faults in muscle protein synthesis or degradation to combat age-related muscle dysfunction.
The paper is available at http://www.fasebj.org/content/early/2017/08/30/fj.201700531R.abstr