A muscle can be described in two ways: as an engine that moves the bones, and as secretory tissue that releases proteins into the blood while it works. The second description points to myokines, signals that reach the liver, bones, fat tissue and the immune system. Find out what the data actually say about this mechanism and where the firm conclusions end.
Key facts about myokines:
- Proteins and peptides produced by skeletal muscle cells
- Local and distant action – within the muscle, around it or in far-away organs
- Contraction is not required for every one of these molecules, although exercise clearly shifts their levels
- A short window of increase – the clearest changes appear up to roughly an hour after exercise
- No routine test that would assess a patient’s “myokine level”
What are myokines?
Myokines are bioactive proteins and peptides released by skeletal muscle cells. Some circulate in the blood and act on distant organs, others stay inside the muscle. The best-described ones include interleukin 6, interleukin 15 and myostatin, a protein that restrains fibre growth.
Contraction is not a necessary condition for all of these molecules. Several appear at rest as well, and exercise alters the pace of release rather than the muscle’s ability to produce them. It is therefore more accurate to speak of a shifting secretion profile than of a switch flipped by training.
How do muscles release myokines during movement?
A working fibre releases signalling molecules into the space between cells, and some of them pass into the capillaries and circulate in plasma. The stimulus comes from changes inside the cell during contraction: energy use, mechanical tension and calcium ion flow.
Why are muscles called a hormonal organ?
The phrase refers to function rather than structure. Muscles as secretory tissue send substances into the blood that change how other tissues behave. The concept was introduced by Bente Klarlund Pedersen of the University of Copenhagen and Mark Febbraio, who described interleukin 6 released by working fibres. It is a useful but imprecise analogy. Not every myokine circulates in blood, and not every one meets the definition of a hormone.
Tissues reached by signals from muscle:
- Liver – glucose and lipid handling
- Fat tissue – the pace of energy release and storage
- Bone – remodelling of bone tissue
- Immune system – the balance of inflammatory signals
- Nervous system – a direction still studied mainly in animal models
How do myokines act on the whole body?
Myokine action comes down to changing how target cells behave. Glucose and lipid handling, mitochondrial function, remodelling of muscle tissue and the immune response. The strength of that link, though, differs between molecules.
No single molecule can currently be credited with all of these effects. The impact of movement on health is measured with whole-body indicators such as VO2 max as a predictor of lifespan, because they capture the sum of changes in circulation, muscle and metabolism.
How do myokines affect inflammation and ageing?
Exercise shifts the inflammatory profile in a less pro-inflammatory direction, although there is no proof that myokines alone are responsible. A meta-analysis of 11 randomised trials (n=1135) by Poorhabibi and colleagues from Allameh Tabataba’i University and the university hospital in Zurich reported in 2025 a drop in CRP and TNF-alpha, proteins that drive inflammation, after training alongside a temporary rise in interleukin 6, with wide variation between the studies.
A temporary rise in interleukin 6 after exercise has a different basis from its persistently raised level in chronic disease. Brief spike after training does not mean inflammation is worsening. The link between myokines and inflammation touches the processes described as chronic inflammation and ageing, yet crediting them with slower ageing goes beyond the available evidence.
Myokines and muscle loss with age
In an ageing muscle, the balance between growth-promoting and growth-restraining signals shifts. There is no simple rule that less muscle mass means less of every myokine, because the profile also depends on age, inflammation, fat tissue and coexisting illness. The condition described as sarcopenia and muscle loss with age moves that profile in several directions at once.
What changes in the signalling of an ageing muscle:
- A smaller source of signals – lost mass limits the pool of cells able to secrete
- A shift towards restraint – molecules that block fibre growth gain importance
- Response to resistance training – myostatin levels may fall slightly, though certainty around that finding remains very low
- No single marker – the profile cannot be reduced to one laboratory result
Which training best stimulates myokine release?
No single type of training has been established as the strongest stimulus for all myokines. A review of 62 studies (n=1193) by Bettariga and colleagues from Edith Cowan University, published in 2024, found that aerobic and resistance work altered levels of interleukin 15, irisin and decorin to a similar degree, and most differences between modes were not statistically significant. Participants were largely young adults, so extending the conclusions to people in their sixties remains limited.
What determines the size of the response:
- The specific molecule – each has its own kinetics and its own trigger
- Intensity and duration – a short, light stimulus can stay undetectable in blood
- Muscle mass involved – the more fibres at work, the stronger the signal
- Timing of the blood sample – the same session reads differently after 20 minutes and after 4 hours
Kinetics matter as much as the stimulus itself. The largest changes appear straight after exercise and up to roughly an hour afterwards, and within a few hours values usually return to baseline. Muscle mass, the source of these signals, is best maintained through regular strength training after 40.
Myokines – key findings from muscle research
The communication itself remains the best documented part. A working muscle releases proteins that change how other tissues operate. The roles of individual molecules and the effect of particular training formats are described far less firmly, and the connection between muscle and longevity rests today on indirect reasoning. No human study has shown that a single myokine extends life.
This material is educational and does not serve to assess anyone’s health or to select training loads. Before changing your diet or lifestyle, consult a doctor, and with chronic conditions agree with them on a safe range of physical activity.
FAQ: Frequently asked questions about myokines
Are myokines released during every kind of movement?
Every muscle contraction changes signalling, but a measurable rise in blood levels depends on intensity, duration and the particular molecule.
Can myokine levels be tested?
Individual molecules are measured in research projects, whereas a routine clinical panel assessing a “myokine level” does not exist.
How quickly do myokines appear after training?
The largest changes are recorded up to roughly an hour after exercise, so a blood sample taken later won’t show what the training actually triggered.
Does walking stimulate myokines too?
Moderate-paced walking can raise interleukin 6, but in a study by Kistner and colleagues at Harvard (2024, n=13) the rise appeared only after two to three hours of walking.
Are myokine levels lower with a small muscle mass?
It can’t be reduced to a simple ratio: what determines myokine output is more than muscle mass alone.
References:
- Gu H. et al. (2026). Key hormones for the control of muscle mass: Myokines. Best Practice & Research Clinical Endocrinology & Metabolism. https://doi.org/10.1016/j.beem.2026.102115
- Poorhabibi H. et al. (2025). Short-Lived Exercise-Induced Exerkines Modulate Inflammation. Biomolecules. https://doi.org/10.3390/biom15111590
- Bettariga F. et al. (2024). Exercise training mode effects on myokine expression. Journal of Sport and Health Science. https://doi.org/10.1016/j.jshs.2024.04.005
