Muscle Week: “Sarcopenia is a major public health issue”

On the occasion of the second edition of Muscle Week, labeled Grande Cause Nationale 2024, organized by AFM-Téléthon and the Institute of Myology from June 1 to 7, 2024, France Pietri-Rouxel, Director of Research at the CNRS at the myology research center-Sorbonne University-Inserm-Institute of Myology, takes stock with Pourquoi Docteur on a relatively little-known muscle disease: sarcopenia.

Why Doctor: What is sarcopenia?

France Pietri-Rouxel : From a physiological point of view, we are all subject to a decrease in muscle mass and strength with age. We lose between 1 and 2% of muscle mass from the age of 25/30. This can be compensated for with endurance exercise. But this process is well underway. The number and size of muscle fibers decrease until the age of 60 and it accelerates thereafter.

This age-related physiological decline can be excessive in some people and it becomes pathological. This pathology is called sarcopenia. It was declared a disease by the WHO in 2016. Its definition, revised in 2019, indicates that it is a muscular disease linked to aging that is characterized by an excessive loss of muscle mass, strength and quality that leads to an alteration of physical performance.

With sarcopenia, the risk of falling – the leading risk of accidental death in those over 65 – is increased. There is also an increase in hospitalization times and an increased risk of loss of autonomy.

Sarcopenia is a major public health issue. About 15% of people over 65 suffer from sarcopenia. The forecast for 2045 is for a 68% increase in cases with about 32 million people affected worldwide. This increase is linked to the aging of the population as well as the increase in obesity rates and the sedentary lifestyle of young people. Indeed, if you do not exercise, muscle capital is less important when you start to lose mass.

Sarcopenia: “one of the first signs is loss of walking speed”

What are the signs of sarcopenia?

A reduction in walking speed should be a warning sign. For example, taking longer to get to and from the bakery than before. The first muscles affected by the disease are those in the legs. The quadriceps are the most affected by sarcopenia. This is why one of the first signs is a loss of walking speed.

However, the main complaint heard from patients is loss of strength, because this is what most disrupts their daily lives. They notice, for example, having difficulty carrying their groceries or a pack of water. This loss of physical strength is really exaggerated compared to a person of the same age who would not be sarcopenic. Falls and difficulty getting up from a chair or armchair are also signs.

How is this muscle disease diagnosed?

It should be noted that sarcopenia is very poorly diagnosed. Unfortunately, treating physicians are poorly trained in muscle health. Although we are made up of 40% muscle, there is no specific myology module. Muscle pathologies are studied at the same time as neurology. In addition, sarcopenia is a disease that is little known to the general public. Patients and their loved ones often think that the observed declines in physical performance are related to age. Thus, patients often come to the doctor for Alzheimer’s or diabetes, and the disease is discovered.

Another problem: the diagnosis is complex because it is multifactorial: an MRI, a strength test, a walking test must be done and then the results correlated.

We said to ourselves that to fix “what is not working well”, it was enough to increase the GDF5 rate.

The causes of this disease, which leads to excessive loss of muscle mass and strength, remain relatively unknown, but you and your team have recently made a major discovery.

We know that a muscle contracts because there is a symbiotic association with a motor neuron. This nerve, which has a motor function, is connected to the muscle and allows the excitation-contraction coupling. If this mechanism does not work well, the muscle does not do well. This “dysfunction” can be linked to a neuromuscular disease, prolonged immobilization or aging.

A Franco-Italian team demonstrated for the first time in 2013 that the body has a system in place to combat excessive atrophy. They discovered that if the activity of the GDF5 protein is stopped, the muscle disappears. It thus plays a role in maintaining muscle mass.

My team and I wondered what the missing link is between the muscle that senses that there is an electrical alteration and this GDF5 that comes to fight against atrophy. We then identified a protein called CaVβ1E. It is normally expressed in the embryo, and is not very present in adults. However, under certain conditions, particularly denervation, it will express itself again and activate the expression of GDF5 to counter muscle loss.

In a study with mice, it was demonstrated that this CaVβ1E/GDF5 link is no longer as effective with aging and that excessive atrophy can no longer be prevented. The human CaVβ1E analogue has also been identified and a correlation between CaVβ1E expression in human muscles and age-related decline in muscle mass has been shown.

Given these results, we thought that to fix “what is not working well”, it was enough to increase the level of GDF5 because it is a circulating protein and easy to administer. We carried out a chemical synthesis of this protein – a bit like insulin – and we administered it to old mice for 4 months. We observed an increase in mass and strength in them and we had a preservation of the neuromuscular junction. This did not cure sarcopenia when it was established, but it prevented it from getting worse if the product was administered at its beginnings.

Is this discovery used in the clinic?

There is still research to be done. We are currently defining the dose and the best routes of administration. We hope – if all goes well – that phase 1 clinical trials can take place in 2026.

We also plan to study whether GDF5 can be used against neuromuscular diseases such as Duchenne muscular dystrophy or ALS, which is a pathology of motor neurons. There could also be an application for patients in intensive care. Indeed, when people are placed on a ventilator, the diaphragm, which is also a muscle, atrophies. Recovery is very long if this occurs.

The idea of compensatory response to atrophy – even though it was discovered in 2013 – is still quite new. We are really pioneering in being able to use this compensatory mechanism in an application for aging or diseased muscle.

“You have to take care of your muscles all your life”

Do you have any advice for taking care of your muscles and preventing the effects of aging?

You have to take care of your muscles throughout your life. Since muscle mass decreases from the age of 25/30, it is better to start with a slightly larger muscle mass. Resistance training – something that more and more young people are doing in the gym today – is one of the best ways to limit the loss of muscle mass linked to age. Even if the degradation will occur, it will be less serious.

However, to help your muscles stay healthy, you don’t have to make a big effort. You just have to be active. We often forget this, but walking is a physical activity.

Moreover, dancing is particularly recommended for the elderly. It provides physical activity and is also beneficial for memory, tone, coordination and inflammation levels.