It is tempting to understand muscle’s role in the body as a simple mechanical motor. But the truth is much more complex: our muscles function as an endocrine organ that can influence virtually every system in our bodies.
When a muscle contracts, hundreds of molecules known as myokines – substances essential for the body to function properly – are released. Their discovery transformed modern physiology, giving rise to the idea that “exercise is medicine”.
But this concept falls short. In reality we can go much further, and say that exercise is as necessary for our health as breathing or eating, while a sedentary lifestyle and lack of movement can be classified as a source of illness.
What are myokines?
Myokines are hormones that communicate via the bloodstream with various organs such as the brain, adipose tissue, liver, bone and the immune system. According to a 2024 review, they are the reason why exercise is beneficial for the immune system.
The most widely studied myokine to date is interleukin-6 (IL)-6. While it is released at rest, it is released at levels up to 100 times higher during high-intensity or aerobic endurance exercise. Also of importance are irisin, which is key to maintaining body fat balance, and brain-derived neurotrophic factor (BDNF), which is involved in neuroplasticity and cognitive function.
Exercise also stimulates other organs to release exerkines, which are equally important. A 2022 review revealed the role that these molecules play in cardiovascular, metabolic, immune and neurological health. If we are inactive – meaning few exerkines circulate in our bodies – the risk of disease and all-cause mortality increases.
Molecules that benefit the entire body
Myokines act in different ways in different parts of the body:
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Immune system: Recent publications identify at least nine myokines that influence the proper functioning of the immune system. These include irisin, decorin and the interleukins IL-6, IL-7 and IL-15. Their release during exercise promotes the proliferation and differentiation of our immune cells, enhancing immune surveillance.
They also reduce chronic systemic inflammation, a key factor in preventing many metabolic and cardiovascular diseases. IL-6, for example, acts as an anti-inflammatory signal that can regulate the activity of lymphocytes, macrophages and NK cells.
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Nervous and neurocognitive system: Muscle exerts a direct influence on the brain via what has been termed the “muscle-brain axis”. Evidence shows that molecules such as BDNF, irisin and cathepsin B can stimulate the formation of new neurons. They are also linked to improved learning and memory, and are associated with protection against the cognitive decline associated with neurodegenerative diseases.
Irisin, for instance, has been linked to increased levels of BDNF in the hippocampus, a region crucial for memory. And cathepsin B contributes to neuronal regeneration and improved cognition.
This set of chemical signals explains why physically active people have a lower risk of cognitive decline and better emotional health. The brain “listens” to what the muscles are saying when they contract, and responds by adapting and becoming stronger.
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Glucose and fat metabolism: During exercise, IL-6 plays a key role in mobilising fatty acids from adipose tissue, primarily visceral fat (which accumulates in the abdominal cavity and poses a greater risk). This promotes fat burning and helps maintain blood glucose levels.
It also regulates insulin sensitivity, enabling the muscle to take up glucose more efficiently. This mechanism explains some of the benefits of exercise in preventing type 2 diabetes. Overall, muscle acts as a “metabolic thermostat” that regulates energy expenditure and determines when to mobilise, store or use energy depending on physical activity.
Read more:
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Cardiovascular system: Although exercise for cardiac patients should be prescribed by a healthcare professional such as a cardiologist or physiotherapist, it can help prevent cardiovascular disease. Physical activity triggers the release of exerkines which promote vasodilation, improve vascular function, and reduce arterial stiffness.
This explains why physically active people have a lower risk of high blood pressure, coronary heart disease and heart failure.
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Bones and osteoporosis: Muscles also interact with the skeleton. Multiple myokines promote bone formation and remodelling by stimulating the activity of osteoblasts (bone-forming cells) and regulating bone mineral density. This is a necessary complement to the mechanical stresses of exercise, and to prevent and combat osteoporosis.
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Tumour suppression and reduced cancer risk: An article published in The Lancet Oncology identifies a sedentary lifestyle as a risk factor for more than 10 types of cancer. This is partly explained by the fact that during exercise, myokines are released which inhibit the spread of cancer cells and reduce DNA damage from potentially malignant cells.
To this we can add exercise’s ability to mobilise the immune cells capable of recognising and destroying tumour cells in the early stages of growth. Even one session of exercise significantly increases the levels of myokines capable of suppressing the growth of cancer cells.
Taken together, all this evidence shows that our muscles act as an endocrine organ. Every single muscle contraction sends signals that regulate the body’s internal balance – meaning movement is biologically necessary for our bodily systems to function properly.
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