How muscles ‘talk’ to your body

We all know that exercise is good for us. A sea of scientific research has proven beyond a doubt that it protects our physical and mental health.

Though we’ve known about the benefits of exercise for many years, it’s taken longer to figure out exactly how it helps.

Many mechanisms are involved, but scientists have recently discovered a new piece of the puzzle: myokines.

What are myokines?

In the past, we thought of muscles as machines that helped us lift things, stand up straight, chew, and so on. But, as it turns out, they’re much more complex.

Scientists have now shown that muscles are endocrine organs – they release hormones and other compounds that communicate with all your body’s systems. These compounds are collectively called “myokines.”

Skeletal muscles, which connect to bones and help you move, release myokines when they contract.

Researchers have already identified more than 650 myokines, so it will take time to discover precisely how they all influence your health. But what scientists have discovered already is fascinating.

Below, we’ll explore some of the theories and discoveries to date. In particular, we’ll look at myokines’ influence on inflammation, brain health, and bone health.

Before we get started, we should note that much of the research so far has been on animals. 

Animal studies are an important stage of the scientific process, but we have to be cautious about applying the findings to humans — we’re not just oversized mice.

Inflammation and metabolism: IL-6

One of the first myokines identified was interleukin-6 (IL-6). When you exercise, your muscles pump it into your blood, causing levels to rise 100-fold

Interestingly, IL-6 is usually associated with increased inflammation, but it has an anti-inflammatory effect when muscles release it. 

It also helps your body produce other anti-inflammatory compounds, while blocking the production of compounds that promote inflammation.

Because low-level inflammation is linked to a wide range of chronic diseases, IL-6 likely plays a part in some of the beneficial effects of exercise.

Inflammation aside, IL-6 also influences your metabolism.

For instance, it has a positive effect on blood sugar levels by helping insulin move sugar away from your blood and into your muscles. It may also encourage your pancreas to release more insulin.

Storing excess fat around your belly is linked to poorer health, but exercise helps get rid of it. And there’s some evidence that IL-6 released from muscles may be part of the reason why.

The muscle-brain connection

Regular exercise is linked to better mental health, reduced dementia risk, and other benefits. Though scientists are still investigating these connections, myokines seem to factor in.

For instance, animal studies suggest that a myokine called cathepsin B is released from muscles when you run.

It enters the bloodstream and travels to the brain, where it stimulates the release of brain-derived neurotrophic factor (BDNF). 

BDNF helps brain cells grow and survive and plays a part in learning and memory.

Another myokine, called irisin, may also help increase BDNF levels in the brain.

The links between exercise and brain health likely involve many mechanisms working together, but cathepsin B, irisin, and other myokines seem to be key. 

Muscle talking to bone

Muscles and bones are closely linked. Like muscles, bones are living tissues that the body continually remodels and repairs. 

When you exercise, your muscles put an extra load on your bones. This mechanical stress stimulates bone growth and repair.

Meanwhile, muscles communicate with bones via myokines. 

Animal studies suggest that a myokine called myostatin influences bone health.

At high levels, myostatin prevents bone growth, while IL-6 and other myokines appear to promote new bone growth.  

What should you do?

We’ve only looked at myokines’ influence on a few body systems here. There’s growing evidence that these compounds play a part in maintaining the health of your blood vessels, immune system, liver, and skin, too.

The take-home message is that your body is a wonderfully complex machine, and keeping active and using your muscles will support the health of your whole body.

You don’t need to go to the gym every day or bench press 400 pounds. Running and even walking are great. 

Try to fit exercise into your life in a sustainable way – get into the habit of walking rather than driving, taking the stairs rather than the elevator, or getting off the bus a few stops early. 

Eventually, it’ll become a healthy habit that you do automatically. Then, your myokines will take care of the rest.

In a recent ZOE Science & Nutrition podcast episode, we spoke with Prof. Karyn Esser, chair of the Department of Physiology and Aging at the University of Florida. She spoke about the importance of healthy muscles as we age. So, if you’d like to learn more, try that next.


Brain-derived neurotrophic factor and its clinical implications. Archives of Medical Science. (2015). 

Effects of myokines on bone. Bonekey Reports. (2016). 

Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metabolism. (2012). 

Exercise and dementia prevention. Practical Neurology. (2020). 

Exercise-induced changes in visceral adipose tissue mass are regulated by IL-6 signaling: A randomized controlled trial. Cell Metabolism. (2019). 

Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metabolism. (2013). 

Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nature Medicine. (2011). 

Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes. (2006). 

Muscle as an endocrine organ: Focus on muscle-derived interleukin-6. Physiological Reviews. (2008). 

Muscle–organ crosstalk: The emerging roles of myokines. Endocrine Reviews. (2020). 

Myokines and resistance training: A narrative review. International Journal of Molecular Sciences. (2022). 

Myokines: Discovery challenges and therapeutic impediments. The Journal of the Pakistan Medical Association. (2019). 

Myokines: The endocrine coupling of skeletal muscle and bone. Advances in Clinical Chemistry. (2020). 

Myostatin is a direct regulator of osteoclast differentiation and its inhibition reduces inflammatory joint destruction in mice. Nature Medicine. (2015). 

Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. The Journal of Physiology. (2000). 

Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Annals of Internal Medicine. (2000). 

Running-induced systemic cathepsin B secretion is associated with memory function. Cell Metabolism. (2016).