Danish professor heads up successful hunt for ‘body builder protein’

The discovery may help explain certain types of muscular weakness, myopathy. In time, it could potentially be used to rebuild muscle mass in elderly and people with significant muscular weakness. And all without having to lift a finger.

How do muscles know to grow with hard use?

This question has been a topic of study by an international team of scientists. And the research of these 30 scientists, conducted with funding from the Lundbeck Foundation, has led to a surprising discovery presented in an article recently published in scientific journal EMBO Journal.

According to the study:

When our muscles work hard for short intervals – for instance when lifting weights at the gym – a signal protein (the ZAK-beta protein) sends a message to the muscles that they should convert the exertion to growth.

And it is this particular signal that causes the muscles to grow, explains Professor Simon Bekker-Jensen, head of the research team at the University of Copenhagen’s Centre for Health Aging:

‘Scientists have been searching for this answer for a great many years, so it’s extremely satisfying that we’ve managed to find it. Also because it comes with huge potential for the development of medicines to build muscle mass in elderly and people with significant muscular weakness – without having to lift a finger,’

 

Detective work

The story about how Simon Bekker-Jensen and his colleagues got on the track of the signal protein began – as is so often the case in the world of research – when they read about a discovery made by another team of researchers.

These colleagues had closely examined six patients with a specific type of muscular weakness (myopathy), explains Simon Bekker-Jensen:

‘They observed that the patients all had a mutation in one gene called ZAK – a gene that codes for the ZAK-beta protein. When we read their scientific article, we asked ourselves: What is the link between the ZAK gene and the fact that these six patients were unable to build sufficient muscle mass? And so we decided to take a closer look at what the ZAK gene does. Including how the ZAK-beta protein works.’

This detective work was conducted with the help of a series of experiments on mice that were genetically altered to develop the same mutation in the ZAK gene as was observed in the six myopathy patients.

In these experiments, the scientists stimulated the muscles in the genetically altered mice corresponding to if the animals had actually lifted weights.

The scientists then measured whether the muscle stimulation caused the genetically altered mice to ‘switch on’ the muscle-building signals at the molecular level.

It did not.

However, a group of control mice without the mutation in the ZAK gene which underwent the exact same experiment did respond by switching on the muscle-building signals.

This demonstrated a link between a normally functioning ZAK gene and muscle growth.

A ‘body builder protein’

The discovery presented in the article in EMBO Journal opened the scientists’ eyes to ‘some exciting perspectives’, which they continue to work on, says Professor Simon Bekker-Jensen:

‘For example, we’ve studied what happens when you over-express the ZAK gene in a normal, non-genetically-altered mouse – that is, when you add very high concentrations of the ZAK-beta protein. And here we made another fascinating observation. In the experiment, the animals didn’t have to do anything – they didn’t move in any way in order to build muscle – and yet, the large muscles in their locomotive apparatus grew by up to 50%. Without lifting a finger! In other words, the ZAK-beta protein works as a kind of “body builder protein” – and that’s the discovery we’re now in the process of analysing in detail. It has some exciting perspectives.’

It is exciting because it could potentially prove useful in connection with developing medicines, according to another University of Copenhagen scientist, Cathrine Nordgaard, a PhD student on the research team and first author of the scientific article in EMBO Journal:

‘If you’ve been bedridden for a period of time, muscle loss is unavoidable – and it occurs relatively quickly. The issue – especially among elderly – is difficulty rebuilding enough muscle to regain mobility – because they simply don’t have the strength to work out. In these cases, it would be fantastic if it were possible to over-express the ZAK gene – and thereby add high concentrations of the “body builder protein” – causing the muscles to grow. This would mean the muscles could do some of the initial work towards increasing the degree of function.’

The team of researchers has now started investigating this aspect, says Cathrine Nordgaard: ‘Hopefully, it’s possible, be it will be many years before we’re there. This isn’t something that’s just around the corner.’

Read the article in EMBO Journal

The team behind the article in EMBO Journal comprises scientists from Denmark, the UK, Netherlands, Finland, France and Austria.

Funding for the project has been provided by the Lundbeck Foundation, together with the Novo Nordisk Foundation and the European Research Council.