The idea that muscle is a simple mechanical motor has become obsolete thanks to a discovery that has changed modern physiology: in reality, it functions as an endocrine organ capable of influencing virtually all the systems of our body.

During muscle contraction, hundreds of molecules called myokines are released, substances essential for the body to function correctly. This is where the idea that “exercise is medicine” originated . However, this concept has also fallen out of fashion. In reality, we should go further and say that it is as necessary for our health as breathing or eating, while a sedentary lifestyle and lack of movement are a source of illness.

What are myokines?

Myokines act as hormones that communicate via the bloodstream with various organs, including 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 studied myokine to date is interleukin-6 (IL-6) , which is released during high-intensity or aerobic endurance exercise up to 100 times more than at rest. Irisin , key to maintaining body fat balance, and brain-derived neurotrophic factor (BDNF) , involved in neuroplasticity and cognitive function, are also important.

And before focusing on the effects of this family of molecules, it’s important to note that movement also stimulates other organs to release the equally important exerkins . For example, a 2022 review reveals their role in improving cardiovascular, metabolic, immune, and neurological function. If we are sedentary and few exerkins circulate throughout our bodies, the risk of disease and mortality from all causes increases.

Torrent of beneficial molecules

Below we break down how myokines act in different parts of our body:

• 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, thus enhancing immune surveillance.

  Furthermore, they reduce chronic systemic inflammation, a key factor in the prevention of many metabolic and cardiovascular diseases. IL-6, for example, acts as an anti-inflammatory signal capable of modulating the activity of lymphocytes, macrophages, and NK cells.

• Nervous and neurocognitive system . Muscle exerts a direct influence on the brain through what has been called the “muscle-brain axis.” Evidence shows that molecules such as BDNF, irisin, and cathepsin B can stimulate the formation of new neurons. They also have an effect on improving learning and memory and are associated with protection against cognitive decline in neurodegenerative diseases .

  For example, irisin has been linked to an increase in BDNF in the hippocampus, a region crucial for memory. In turn, cathepsin B contributes to neuronal regeneration and improved cognition.

  This set of chemical signals explains why active people show a lower risk of cognitive decline and better emotional health: the brain “listens” to what the muscles say when they contract, and responds by adapting and strengthening.

• Glucose and fat metabolism. During exercise, IL-6 plays an essential role in mobilizing fatty acids from adipose tissue, primarily visceral adipose tissue (which accumulates in the abdominal cavity and poses the greatest risk). This promotes fat burning and contributes to maintaining blood glucose levels.

  It also modulates insulin sensitivity, allowing 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 adjusts energy expenditure and determines when to mobilize, store, or use energy based on physical activity.

• Cardiovascular system . Although exercise in cardiac patients should be prescribed by a healthcare professional such as a cardiologist or physiotherapist, it can be very beneficial for preventing cardiovascular disease . Physical activity induces the release of exerkins that promote vasodilation, improve vascular function, and reduce arterial stiffness. This explains why physically active people have a lower risk of hypertension, coronary heart disease, and heart failure.
• Bones and osteoporosis . Muscle also interacts with our skeleton. Several myokines promote bone formation and remodeling, stimulating the activity of osteoblasts (bone-building cells) and modulating bone mineral density . This is a necessary complement to the mechanical loads of exercise to prevent and combat osteoporosis.
• Tumor control and cancer risk reduction . An article published in The Lancet Oncology links sedentary lifestyles to more than 10 types of cancer as a risk factor. This is partly explained by the fact that myokines are released during exercise, inhibiting the proliferation of cancer cells and reducing DNA damage in potentially malignant cells.

  In addition, it has the ability to mobilize immune system cells capable of recognizing and destroying tumor cells in their early stages . A single exercise session significantly increases levels of myokines with the potential to suppress the growth of cancer cells.

Taken together, all this evidence demonstrates that muscle functions as a true endocrine center: each muscle contraction sends signals that adjust the body’s internal balance, confirming that movement is a biological necessity for our body systems to function properly.

Author Bios: Beatriz Carpallo Porcar is a Physiotherapist. Teaching and research staff member in the Physiotherapy degree program at San Jorge University. Member of the iPhysio research group, San Jorge University, Andrés Ráfales Perucha is a Physiotherapist and Teaching and Research Staff at San Jorge University. Member of the UNLOC research group, Daniel Sanjuán Sánchez is a Physiotherapist and research lecturer at the Faculty of Health Sciences at San Jorge University; Associate Professor at the Faculty of Nursing and Physiotherapy, University of Lleida. Member of the iPhysio research group, San Jorge University, José Lesmes Poveda López is Professor of Physiotherapy at San Jorge University and Paula Cordova Alegre is on the Teaching and research staff in the physiotherapy and nursing degrees at San Jorge University at San Jorge University