For decades, muscles were primarily viewed as structures responsible for movement, posture, and physical strength. In traditional biology, they were often compared to mechanical motors that simply converted energy into motion. However, modern scientific discoveries have completely transformed this understanding. Researchers now recognize that skeletal muscles function as a highly active endocrine organ capable of influencing nearly every major system in the human body.
When muscles contract during physical activity, they release hundreds of signaling molecules known as myokines. These molecules travel through the bloodstream and communicate with organs such as the brain, liver, adipose tissue, bones, heart, and immune system. Their discovery has revolutionized exercise physiology and strengthened the scientific foundation behind the popular phrase “exercise is medicine.”
Yet many scientists now argue that even this phrase does not fully capture the importance of movement. Exercise is not merely a treatment or preventive strategy; it is a biological necessity, as essential for human survival and long-term health as proper nutrition and breathing. Conversely, physical inactivity and sedentary behavior are increasingly being recognized as major contributors to chronic disease and premature death.
Understanding Myokines and Exerkines
Myokines are hormone-like substances produced and released by skeletal muscles during contraction. These molecules act as messengers that allow muscles to communicate with other organs throughout the body. Their release increases significantly during physical activity, especially during aerobic and endurance exercise.
One of the most studied myokines is interleukin-6 (IL-6). Although IL-6 exists in the body at low levels during rest, exercise can increase its concentration up to 100 times. Unlike inflammatory IL-6 released during illness, exercise-induced IL-6 often acts in anti-inflammatory and metabolically beneficial ways.
Other important myokines include:
- Irisin, which helps regulate body fat balance and energy expenditure
- Brain-derived neurotrophic factor (BDNF), which supports learning, memory, and neuroplasticity
- Cathepsin B, linked to neuronal regeneration and improved cognitive function
- Decorin, associated with muscle growth and immune regulation
Exercise also stimulates the production of other signaling molecules called exerkines, which originate from organs beyond skeletal muscle. These compounds influence cardiovascular, metabolic, neurological, and immune health. According to scientific reviews, low levels of physical activity reduce the circulation of these beneficial molecules, thereby increasing the risk of chronic disease and all-cause mortality.
Exercise and Immune System Function
One of the most important discoveries in modern exercise science is the relationship between physical activity and the immune system. During exercise, muscles release myokines that regulate immune cell activity and strengthen the body’s defense mechanisms.
Research has identified several myokines — including IL-6, IL-7, IL-15, irisin, and decorin — that promote the proliferation and differentiation of immune cells such as lymphocytes, macrophages, and natural killer (NK) cells. These immune cells play essential roles in detecting infections and destroying harmful or abnormal cells.
Exercise also reduces chronic systemic inflammation, which is considered a major underlying factor in conditions such as obesity, cardiovascular disease, diabetes, and certain cancers. Exercise-induced IL-6 acts as an anti-inflammatory signal that can regulate immune responses and suppress inflammatory cytokines.
This explains why physically active individuals generally experience lower rates of chronic disease and often recover more effectively from infections and inflammatory conditions.
The Muscle–Brain Axis
Modern neuroscience has revealed a fascinating biochemical communication system known as the “muscle-brain axis.” During exercise, muscles release signaling molecules that directly influence brain structure and function.
Among the most important of these molecules is BDNF, often referred to as “fertilizer for the brain.” BDNF supports the survival of neurons, stimulates the formation of new neural connections, and enhances neuroplasticity — the brain’s ability to adapt and learn.
Irisin also contributes to brain health by increasing BDNF levels in the hippocampus, a region essential for memory and learning. Meanwhile, cathepsin B has been associated with improved cognitive performance and neuronal regeneration.
These chemical signals help explain why regular physical activity is associated with:
- Improved memory and concentration
- Better emotional regulation
- Reduced anxiety and depression
- Lower risk of dementia and Alzheimer’s disease
- Protection against age-related cognitive decline
The brain essentially “listens” to the muscles during movement and responds by strengthening neural pathways and improving overall cognitive resilience.
Regulation of Glucose and Fat Metabolism
Skeletal muscle plays a major role in regulating metabolism and maintaining energy balance. During exercise, muscles require large amounts of energy, triggering complex biochemical responses that improve the body’s ability to process fats and glucose.
IL-6 stimulates the release of fatty acids from adipose tissue, particularly visceral fat stored around abdominal organs. This promotes fat oxidation and helps maintain healthy blood glucose levels during physical activity.
Exercise also improves insulin sensitivity, enabling muscle cells to absorb glucose more effectively from the bloodstream. This mechanism significantly reduces the risk of insulin resistance and type 2 diabetes.
In this way, skeletal muscle functions as a “metabolic thermostat,” determining when energy should be stored, mobilized, or utilized depending on the body’s physical demands.
Cardiovascular Protection Through Exercise
Cardiovascular disease remains one of the leading causes of death worldwide. However, regular physical activity has consistently been shown to reduce the risk of heart disease and improve vascular health.
Exercise stimulates the release of exerkines that promote vasodilation, improve endothelial function, and reduce arterial stiffness. These changes improve blood circulation and decrease strain on the heart.
Physically active individuals generally have lower risks of:
- Hypertension
- Coronary artery disease
- Stroke
- Heart failure
- Atherosclerosis
Additionally, exercise improves lipid metabolism, reduces harmful cholesterol accumulation, and enhances overall cardiovascular efficiency.
Although exercise programs for individuals with heart disease should be supervised by healthcare professionals, physical activity remains one of the most effective tools for preventing cardiovascular disorders.
Bone Health and Osteoporosis Prevention
The relationship between muscles and bones extends far beyond mechanical movement. Muscles release myokines that influence bone metabolism and stimulate the activity of osteoblasts — the cells responsible for bone formation.
Regular physical activity increases bone mineral density and strengthens skeletal structure, helping prevent osteoporosis and fractures, especially in older adults.
Weight-bearing exercises such as walking, resistance training, and running are particularly effective because they combine mechanical loading with beneficial biochemical signaling between muscles and bones.
Exercise and Cancer Prevention
Growing evidence suggests that physical inactivity increases the risk of multiple forms of cancer. Researchers have identified sedentary behavior as a significant risk factor for more than ten types of cancer.
Exercise may reduce cancer risk through several biological mechanisms:
- Release of cancer-suppressing myokines
Certain myokines inhibit tumor cell growth and reduce DNA damage in potentially malignant cells. - Enhanced immune surveillance
Physical activity mobilizes immune cells capable of detecting and destroying tumor cells during the earliest stages of development. - Reduced chronic inflammation
Since chronic inflammation contributes to cancer progression, exercise-induced anti-inflammatory effects offer additional protection.
Remarkably, studies show that even a single session of exercise can temporarily increase levels of anti-cancer myokines in the bloodstream.
Sedentary Lifestyle: A Modern Health Threat
The modern lifestyle has drastically reduced daily physical activity. Long working hours, excessive screen time, and limited movement have contributed to a global rise in sedentary behavior.
Scientific evidence increasingly identifies physical inactivity as a direct risk factor for:
- Obesity
- Type 2 diabetes
- Cardiovascular disease
- Osteoporosis
- Depression and anxiety
- Cognitive decline
- Several forms of cancer
A sedentary lifestyle not only weakens muscles but also reduces the production of beneficial myokines and exerkines necessary for maintaining internal physiological balance.
This means that inactivity is not simply the absence of exercise — it is a biological state that actively contributes to disease development.
Conclusion
Modern science has fundamentally changed the way we understand skeletal muscle. Far from being simple mechanical structures responsible only for movement, muscles are now recognized as powerful endocrine organs that communicate continuously with nearly every system in the body.
Through the release of myokines and exerkines, exercise influences immunity, metabolism, brain health, cardiovascular function, bone strength, and cancer prevention. Every muscle contraction sends biochemical signals that help regulate the body’s internal environment and maintain physiological balance.
The evidence clearly demonstrates that exercise is not optional for optimal health. It is a biological necessity deeply integrated into human physiology. Regular movement strengthens the immune system, protects the brain, improves metabolic efficiency, reduces inflammation, and lowers the risk of numerous chronic diseases.
At the same time, prolonged inactivity disrupts these protective mechanisms and increases vulnerability to illness. In today’s increasingly sedentary world, understanding the endocrine role of muscles highlights the urgent importance of incorporating physical activity into daily life.
Ultimately, exercise should not be viewed merely as a lifestyle choice or fitness goal. It is one of the most powerful natural regulators of human health — essential for maintaining both physical and mental well-being throughout life.
References
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