It is not uncommon in science to operate blindly. To use a formula, an equation, theorems without mastering all the subtleties. This is the case of quantum physics, or artificial intelligence for example. The principles of these two disciplines are used all over the world, and at the same time, there are still many gray areas.
Sport has long been shrouded in this mystery. For over a century, physical activity has been recommended left, right and centre in France, from doctors’ surgeries to barroom conversations. And rightly so: its effects on health, against diabetes, Alzheimer’s, cancer and many other pathologies, are no longer in doubt. Without anyone knowing why, precisely, it was beneficial. Until very recently.
For about twenty years – yesterday, on the research scale – discoveries about the internal machinery that is activated during exercise have been accumulating. Beyond its mechanical effect, on blood circulation for example, sports practice leads to a series of molecular reactions that were previously unknown, and that scientists are only just beginning to decipher.
A small revolution: “Beyond expanding our knowledge, this research, most of which is still ongoing, could lead to new ways of treating diseases,” enthuses Cédric Moro, research director at Inserm and author of a collective expert report submitted in 2019 to the Ministry of Sports on the therapeutic benefits of physical activity.
The beginning of a new era
During physical activity, the levels of certain proteins, including cytokines, vary greatly. Changes have been known since the 1990s, but the origins of these changes were only discovered a decade later. Biologists at the University of Copenhagen show that the muscle itself is involved in these changes. Published in the peer-reviewed journal The Physiological Societyin 2000, the discovery shook up the paradigms of the time.
For a very long time, scientists considered muscles as passive tissues, useful for movement, and to support bones, nothing more. The Copenhagen study highlights that they directly produce certain molecules, including one in particular, called Interleukin-VI. “We had a passive, inert vision of muscles. We then understood that we were completely wrong,” continues Cédric Moro. The beginning of a new era.
From then on, scientists realized that the muscle could transform into a gland that provided hormones, in the time of a few pumps. Little by little, biologists realized that other organs functioned in this way, to their great surprise. The heart, the liver, fatty tissues and even neurons are also capable of similar secretions, specific to physical exercise. In 2016, Canadian researchers gave the name “exerkines” to these molecules. A second milestone is set.
“Exerkines”, between sport and enjoyment
Since the 2000s, more than 200 “exerkines” have been identified. A figure that is constantly increasing. Much remains to be discovered about their exact effects. But it is now clear that these substances, which allow certain cells, particularly in the immune system, to “communicate”, play an important role in the benefits of sport. This is notably the conclusion of a literature review published in 2022 in the prestigious scientific journal Nature.
In the presence of these molecules, cells equipped with the right receptors go into “sport” mode. Like in cars, where adjustments make the shock absorbers firmer and the engine more lively. With “cardiokines”, the heart becomes more flexible, more powerful. “Adipokines” help control inflammation or damage caused by exercise. Other “exerkines” modulate the immune response, and so on. Enough to allow the body to endure an effort that puts the organism to the test.
Many of these changes are only temporary, transitory. The molecules released can disappear in less than a day. But in the same way that we gain muscle when we make efforts, their intervention allows us to prepare for the next activity. “Everything suggests that these molecules, and the transformations triggered, end up arming and developing the body,” comments Professor Jacques Hugon, neurologist and Alzheimer’s specialist.
A sport mode, which allows long-term improvements
An “overcompensation” beneficial for health. This is what a team from the University of California, in the United States, showed in 2020. They transferred blood from athletic mice to idle counterparts. Without doing any sport, the latter then saw their brain capacities improve. The study, published in Science, is important: it proves that it is possible, in theory, to benefit from the improvements linked to physical activity just by receiving certain “exerkines”. Enough to suggest that it would be possible to put sport in a capsule, at least, in animals.
In the body, “exerkines” react with each other and transform. So many interactions that make it particularly difficult to interpret their effects. But not for long. In May 2024, a consortium of American scientists, Motrpac, succeeded in producing an initial map of the molecular exchanges that occur during sport in mice. These experiments, revealed in Naturetrace from start to finish some of the paths taken by the body to respond to activity in this animal. A major advance, while most of these chains of actions are still unknown in humans.
Most, but not all. A few of these series of interactions are beginning to give up their secrets. Like those caused by GDF-15a “growth factor”, another family of secretion. In 2020, the Frenchman Cédric Moro showed, with his team from the Institute of Metabolic Diseases in Toulouse, that the molecule helped with lipolysis, the breakdown of fats. Which itself is associated with a better reaction to insulin. Which partly explains why sport is good for diabetics, who suffer precisely from resistance to this hormone.
Putting sport in a capsule?
Researchers are also increasingly interested in irisin. A molecule discovered in 2012 and which, on mice, presents extraordinary effects. Produced by the muscles during exercise, it then passes into the brain. There, in addition to being useful for its functioning, it helps prevent the accumulation of beta-amyloid, a peptide involved in the dysfunctions generated by Alzheimer’s disease. Raising its level could constitute “a new therapeutic strategy”, concludes a study in Nature medicine in 2019.
Many laboratories see this as a possibility, in the long term, of synthesizing the effect of a hike or a 200-meter freestyle swim. These developments could at least lead to pills capable of optimizing certain physiological reactions. But the outcome is uncertain: “What will the body do with these products if it is not in the conditions for physical exercise? It could simply eliminate them, like waste,” qualifies François Carré, cardiologist and sports specialist, professor emeritus at the University of Rennes.
Especially since a pill will not be able to replace the many mechanical effects of sport, which are very useful against cancer, among other things: “Tumors are poorly connected to the blood network, which means that immune cells and treatments do not always reach them. Physical activity, by making the heart beat faster, allows them to be better supplied and improves the effectiveness of treatments,” describes Manon Gouez, researcher at the Léon Bérard center in Lyon and author of a study on the subject published in February 2024 in Frontiers Immunology.
“To stop moving is to deprive ourselves of our natural abilities”
Whether or not they lead to future drugs, this work has already helped to break down many stereotypes. Starting with those surrounding lactic acid. Also an “exerkine”. Perhaps the best known of all. Once reviled by athletes, considered waste, a toxin, this molecule is gradually coming back into favor. “Contrary to what we thought, we should not eliminate it at all. It also triggers a whole series of adaptations,” continues François Carré.
The specialist insists on one point: “What we must remember is that we are programmed to move. All this is based on genes that are only stimulated if we move. To stop is to deprive ourselves of part of our functioning and our capacities to restore, protect and improve the body”, explains the expert. He does not like to say that sport is good for us. Everything suggests that, on the contrary, it is rather doing nothing that is dangerous.
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