Molecular switch may guard against muscle loss


French researchers taking the fight to sarcopenia.


Sarcopenia leads to the loss of mass, strength and quality of the whole musculature from the age of 50.

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By Paul Biegler

Researchers in France have uncovered a molecular switch that may control and one day help reverse sarcopenia, the dramatic loss of muscle seen with ageing.

The condition increases the risk of falls, hospitalisation and death, and was classified as a disease by the World Health Organisation in 2016. Australia followed suit earlier this year.

“Sarcopenia is defined by a progressive and general loss of mass, strength and quality of the whole musculature from the age of 50,” says France Piétri-Rouxel, from the Centre de Recherche en Myologie at Sorbonne Université in Paris.

“It may lead to a decrease of more than 30% of initial muscle mass at the age of 80,” she says.

Piétri-Rouxel, a co-author of the new study published in the journal Science Translational Medicine, explains that muscles have to contract to stay strong, something triggered by the nerves that supply them. The process is called “excitation-contraction” coupling.

But it’s a classic case of use it or lose it – when muscles don’t contract, they simply waste away. That can happen through disuse, if the person is bedridden or has their limb in a cast for example, or if the nerve is damaged.

The muscles do fight back, however, when they are denied stimulation. The body makes more of something called growth differentiation factor 5 (GDF5), which tries to put a floor under the amount of muscle lost.

The team suspected that muscles could be downsizing with age because the GDF5 back up plan fails, so they set about testing the idea in a series of very clever experiments in mice.

First, they snipped the nerve to one of the animal’s leg muscles. That led to an uptick in a protein called CaVβ1E, which has a lot to say about the movement of calcium in muscle cells, something critical for contraction.

But CaVβ1E, they discovered, was multitasking. It was also working to boost GDF5 and stave off muscle wasting.

Could CaVβ1E be underperforming as we get older, they wondered, and be key to the saggy baggy muscle conundrum?

Training their gaze on a mischief of mature mice – the critters were 78 weeks old or 70 in human years – they found CaVβ1E and GDF5 were indeed in short supply compared to younger specimens.

So they injected the rodents with a concoction that increased the two proteins. That jungle juice effectively rescued the muscles from the ravages of age.

“[W]e demonstrated that in ageing muscle this mechanism is impaired and if we over express CaVβ1E or GDF5 we can preserve muscle mass and strength during ageing,” says co-author Sestina Falcone, also from the Sorbonne.

The burning question, of course, is whether the mice results carry over to people. The team had that covered.

Working with snippets of thigh muscle from younger (20 to 42 years) and older (70 to 81 years) people they found that a human analogue of CaVβ1E was failing to pull its weight in the older folk.

“We discovered that CaVβ1E is also expressed in human muscle and that its expression is correlated to ageing and muscle decline also in humans, suggesting that a similar mechanism is conserved among species,” Falcone says.

The researchers write that calorie restriction, which limits cell damage, and exercise are the best way to preserve muscle size and function as you age. But their research could add a new contender, one that targets the actions of CaVβ1E.

“Currently, the perspective of the team is to develop pre- and clinical applications to prevent sarcopenia” says Piétri-Rouxel.

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Paul Biegler is a philosopher, physician and Adjunct Research Fellow in Bioethics at Monash University. He received the 2012 Australasian Association of Philosophy Media Prize and his book The Ethical Treatment of Depression (MIT Press 2011) won the Australian Museum Eureka Prize for Research in Ethics.
  1. https://bmjopen.bmj.com/content/8/11/e021252
  2. https://www.nature.com/articles/d41586-018-02479-z
  3. https://theconversation.com/the-muscle-wasting-condition-sarcopenia-is-now-a-recognised-disease-but-we-can-all-protect-ourselves-119458
  4. https://stm.sciencemag.org/content/11/517/eaaw1131
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425715/
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