Myokines Explained: How Exercising Muscles Communicate with Your Entire Body

Myokines Explained

How active skeletal muscle sends biological signals—and what those signals may mean for metabolism, immunity, the brain, bones and healthy ageing.

Skeletal muscle does far more than move bones. It stores fuel, produces heat, supports glucose regulation and releases signalling molecules that act within muscle or communicate with other tissues. Many of these muscle-derived signals are called myokines.

Myokine research helps explain why exercise can have effects beyond the muscles doing the work. It is also an evolving field: hundreds of candidate molecules have been proposed, methods differ, and findings from cells or animals do not always translate into clear effects in humans.

Key Takeaways

1. Myokines are proteins or peptides produced and released by skeletal muscle that signal locally or to other tissues.

2. Some myokines change with exercise, but the pattern depends on the molecule, activity, intensity, duration, training status and sampling time.

3. Myokines can act within muscle, on nearby cells or through the circulation; not every proposed myokine has a proven distant-organ effect in humans.

4. Muscle-derived interleukin-6 is a well-studied exercise signal whose context differs from persistently elevated inflammatory IL-6.

5. Irisin, BDNF and other popular examples require careful interpretation because their sources, measurement and human effects are not always settled.

6. Exercise benefits cannot be reduced to one molecule, and no food or supplement can reproduce the complete response to movement.

What Exactly Is a Myokine?

A myokine is generally defined as a signalling protein or peptide produced and released by skeletal muscle. The term includes molecules acting back on the same cell, on nearby cells or—when they enter circulation—on more distant tissues.

1. Autocrine signals act on the cell that released them.

2. Paracrine signals act on nearby cells and tissues.

3. Endocrine signals travel through the circulation to more distant targets.

The wider term ‘exerkine’ includes exercise-responsive signals from many tissues, not muscle alone. This distinction matters because a molecule measured after exercise may come from muscle, liver, fat tissue, immune cells, blood vessels or several sources.

Why Muscle Is Called an Endocrine Organ

Skeletal muscle is traditionally described as contractile tissue. Its ability to release circulating signals led researchers to also describe it as an endocrine organ. Yet much muscle signalling is local, helping regulate fuel use, blood-vessel growth, extracellular matrix, repair and adaptation within the exercised tissue.

The endocrine description is valuable, but it should not imply that every muscle-derived molecule travels throughout the body or produces a clinically meaningful effect.

For the broader physiology, read Muscle as an Endocrine Organ.

Exercise Creates a Changing Signal Pattern

There is no single ‘myokine release’. Different activities create different mechanical and metabolic demands. Concentrations can rise, fall or remain unchanged depending on exercise mode, duration, intensity, muscle mass involved, training status, sex, age, food intake and when the sample is collected.

A 2024 systematic review found changes after both aerobic and resistance exercise, but many pooled effects were not statistically significant and heterogeneity limited precise conclusions. Myokines are one part of a much larger exercise response that also includes neural, vascular, hormonal, immune and metabolic changes.

Interleukin-6: Why Context Matters

Interleukin-6, or IL-6, is one of the best-studied exercise-related myokines. Contracting muscle can release IL-6, particularly during prolonged exercise as muscle glycogen becomes lower. In this setting, IL-6 participates in fuel mobilisation and immune signalling.

IL-6 is also produced by immune cells and other tissues during infection and chronic disease. The molecule’s source, concentration, timing and surrounding signals influence its effects. It is therefore inaccurate to label IL-6 simply ‘good’ during exercise or ‘bad’ during inflammation.

Learn more in Inflammation Explained.

Irisin: Interesting, but Often Oversold

Irisin is a peptide derived from the protein FNDC5 and has been investigated in relation to energy metabolism, fat tissue, bone and the brain. Early findings created enthusiasm, but measurement challenges and inconsistent human results produced substantial debate.

Research continues, but current evidence does not justify treating irisin as a measurable ‘exercise hormone’ that explains weight loss, brain health or healthy ageing on its own. A proposed mechanism is not the same as a proven consumer benefit.

BDNF and the Muscle–Brain Story

Brain-derived neurotrophic factor, or BDNF, supports neuronal function and plasticity. Exercise can raise circulating BDNF in some studies, but circulating BDNF has multiple possible sources, including the brain and platelets. Skeletal muscle can express BDNF, where it appears to have important local actions.

It is therefore too simple to say that exercising muscle releases BDNF into the blood to ‘fertilise the brain’. Exercise supports brain health through many routes, including blood flow, metabolic changes, learning, sleep and multiple signalling molecules. Read Why Strength Isn’t Just About Muscle.

Myostatin, IL-15 and Other Signals

Myostatin

Myostatin is a muscle-derived regulator that restrains muscle growth. Its biology is clinically important, but manipulating it is not a simple lifestyle target, and low myostatin is not automatically healthier in every context.

Interleukin-15

IL-15 has been studied in muscle metabolism, immune regulation and communication with fat tissue. Exercise findings vary, and its role cannot be reduced to one outcome.

Apelin, Decorin, Musclin and Others

A growing list of signals is being investigated. Some have strong mechanistic evidence; others remain candidates. This diversity is a reminder that the benefits of exercise emerge from networks, not a single master molecule.

How Myokines Relate to Metabolism

During exercise, muscle must coordinate glucose uptake, glycogen use, fatty-acid oxidation and communication with the liver and fat tissue. Myokines may contribute to these adjustments alongside insulin, adrenaline, blood flow and intracellular signalling.

Regular muscle contraction also improves metabolic health through mechanisms that do not require a distant myokine. Muscle is a major site of glucose disposal, and training changes its enzymes, mitochondria, capillaries and insulin response. Read The Muscle–Mitochondria Connection.

Myokines and the Immune System

A bout of exercise temporarily alters immune and inflammatory signals. Muscle-derived factors can participate in this response, helping coordinate fuel availability, cell traffic and recovery. A 2026 meta-analysis found that several circulating cytokines changed after acute endurance exercise, but responses varied widely with the protocol and participants.

This does not mean every workout ‘boosts immunity’ or that more inflammation is better. Very demanding exercise, illness, sleep loss and inadequate recovery change the context. Exercise should be scaled to the individual.

Myokines, the Brain and Cognition

Muscle-derived exerkines are proposed as one route linking exercise with the brain. Human trials have measured many candidate molecules alongside cognitive outcomes, but a 2025 living systematic review found continuing uncertainty about which factors actually mediate exercise-related cognitive changes.

The practical conclusion remains robust even while the mechanism is debated: physical activity supports health, and learning or balance tasks directly exercise neural systems too. It is premature to prescribe a specific myokine target for memory or mood.

Myokines and Bone

Muscle and bone communicate mechanically and chemically. Loading from muscle contraction is a major signal for bone, while myokines and bone-derived osteokines are being studied as additional messengers. Many detailed pathways are based on experimental models, so consumers should not assume that increasing one myokine will strengthen bone.

Myokines and the Gut

Researchers are exploring muscle–gut communication through immune, metabolic and microbiome-related pathways. Exercise may influence gut microbial composition, while digestion and absorption supply the nutrients muscles require. The integrated mechanisms remain an emerging field.

Read The Gut–Muscle Axis.

Does Every Movement Release Myokines?

Muscle contraction can stimulate signalling, but it is misleading to promise that every stretch or step releases a particular set of ‘beneficial messages’. Some signals respond only to sufficient duration or intensity; others act locally; and many have not been consistently measured in people.

Everyday movement still matters because it contributes to total activity, breaks up sedentary time and uses muscle. Structured aerobic and resistance exercise provide additional, well-established benefits even when the exact myokine response is unknown.

A Practical Movement Framework

1. Accumulate light movement across the day and break up long periods of sitting.

2. Include moderate-to-vigorous aerobic activity on most days as ability allows.

3. Perform muscle-strengthening activity on at least two days each week.

4. Include mobility, balance and coordination activities regularly.

5. Progress training gradually and allow recovery between demanding sessions.

6. Choose activities you can repeat rather than chasing a theoretical ‘best’ myokine workout.

These principles align with current Australian movement guidance; individual ability and health conditions should shape the plan.

Nutrition Supports the Signalling Tissue

Food does not replace myokines. It supplies energy and nutrients that help muscle contract, recover and adapt. A varied dietary pattern can include protein foods, vegetables, fruit, whole grains, legumes, nuts, seeds and suitable fats.

Adequate protein supports muscle protein turnover, while carbohydrate helps fuel and replenish demanding activity. Hydration, vitamins and minerals also contribute to normal physiological function. Read Why Protein and Resistance Training Work Better Together and The Food Matrix Explained.

Where Bone Broth Fits

Bone broth can contribute fluid, flavour and collagen-derived protein. Protein and sodium vary, and collagen is not a complete protein. Bone broth does not release myokines or reproduce the effects of exercise; muscle contraction is the relevant stimulus.

· Bone Broth Benefits: The Complete Guide

· Shop Broth & Co bone broth collection

Recovery Completes the Training Cycle

Myokine concentrations may return towards baseline within hours, while tissue adaptation unfolds over longer periods. Sleep, adequate nutrition, hydration and appropriate spacing help training remain sustainable. Read Why Recovery Matters More Than Ever After 40.

Common Myokine Myths

Myth: Every myokine is a hormone travelling to distant organs

Fact: Many act locally within muscle or nearby tissues. Only some have demonstrated endocrine actions.

Myth: One myokine explains all exercise benefits

Fact: Exercise changes many systems simultaneously, and no single molecule accounts for the full response.

Myth: More intense exercise always creates better signals

Fact: Responses differ by molecule and person. Excessive training can undermine recovery and consistency.

Myth: A supplement can replace exercise-induced myokines

Fact: No supplement reproduces the coordinated mechanical, neural, metabolic and signalling effects of movement.

Frequently Asked Questions

What are myokines?

They are muscle-produced signalling proteins or peptides that can act within muscle, nearby tissues or sometimes through the circulation.

Does walking release myokines?

Walking involves muscle contraction and can influence exercise-related signalling. The specific response depends on pace, duration, fitness, muscle mass used and the molecule measured.

Does strength training release more myokines?

Not universally. Resistance and aerobic exercise produce different and overlapping responses; no mode is greater for every myokine.

Are myokines anti-inflammatory?

Some participate in immune regulation, but myokines do not simply switch inflammation off. Timing, source and physiological context matter.

Can myokines improve brain health?

Several are proposed mediators of exercise–brain effects, but human evidence does not yet identify one proven myokine prescription for cognition.

Can nutrition increase myokines?

Nutrition can influence muscle health and the exercise response, but myokines are not nutrients. A meal cannot replace the signalling created by contraction.

Final Thoughts

Myokines changed the scientific view of muscle from passive machinery to an active signalling tissue. They help connect contraction with local adaptation and, in some cases, communication across organs.

Their discovery does not turn every movement into a guaranteed chemical broadcast or reduce exercise to one molecule. The strongest message is broader: using muscle regularly supports the whole body through mechanical, neural, metabolic and signalling pathways working together.