The Science of Muscle: Discover How Muscles Are Built

Author:

Julio Valero

Published on:

1/2/2025

The Science of Muscle: Discover How Muscles Are Built

The mechanisms of muscle hypertrophy and their application to resistance training.

Schoenfeld (2010)

Over a decade ago, a thorough analysis of the scientific literature laid the groundwork for our understanding of muscle growth. However, constant advances in research have revolutionized our perspective on this topic.

Overview

Muscle hypertrophy, a process still not fully understood, has generated intense scientific debate. Dr. Brad Schoenfeld proposed three key mechanisms: mechanical tension, muscle damage and metabolic stress. Although mechanical tension is the most widely supported, the role of the other two remains a subject of study and controversy.

What's the problem?

While losing weight may be faster, building muscle requires patience and a targeted approach. Hypertrophy, the process of thickening muscle fibers, is critical to muscle growth. Understanding this mechanism allows us to design more effective training and nutrition programs to achieve optimal results. Although hyperplasia has been studied, evidence in humans is limited, so hypertrophy remains the primary goal for those looking to increase muscle mass.

Strengthen your knowledge: Learn the fundamentals of muscle anatomy

Imagine muscle tissue as a building. To understand how it grows and strengthens, we must first understand its bricks and how they are put together. Just as a building is made up of different materials and structures, muscle has levels of organization, from the smallest units to the entire muscle. Let’s start with the most basic level: the sarcomere, which is like a small brick that is repeated throughout the entire muscle structure. The sarcomere, the basic functional unit of the muscle, is like the tiny engine that powers movement. Composed primarily of actin and myosin filaments, these filaments slide past each other during muscle contraction, thereby shortening the sarcomere and, consequently, the entire muscle fiber.

The repetition of these sarcomeres along the myofibril creates the characteristic striated appearance of skeletal muscle. The myofibrils, in turn, are embedded in the sarcoplasm, the cytoplasm of the muscle fiber, and surrounded by the sarcolemma, its plasma membrane.

Several myofibrils group together to form a muscle fiber, which is a multinucleated cell. A bundle of muscle fibers, surrounded by a layer of connective tissue called the endomysium, forms a fascicle. The fascicles, in turn, group together to form the entire muscle, surrounded by an outermost layer of connective tissue called the epimysium.

Muscle fibers are like little factories of movement. Inside them, we find myofibrils, which are responsible for contracting. In addition, there are mitochondria (which produce energy), a sarcoplasmic reticulum (which stores calcium), nuclei (which control the cell) and a liquid called sarcoplasm. The interesting thing is that muscle fibers have many nuclei, unlike other cells that only have one.

Satellite Cells

Satellite cells, often referred to as resident muscle stem cells, are found in a quiescent state within the muscle fiber niche. Upon undergoing an intense and sustained mechanical stimulus, such as strength training, these cells are activated, proliferate, and fuse with existing muscle fibers. This process, known as myogenesis, leads to an increase in the number of nuclei within the muscle fiber.

The myonuclear dominance theory proposes that each muscle nucleus controls a volume of cytoplasm and its protein synthesis capacity. Therefore, an increase in the number of nuclei, thanks to the contribution of satellite cells, allows a greater potential for the synthesis of contractile proteins, such as actin and myosin, essential for muscle growth. This increase in protein synthesis leads to a thickening of the myofibrils and, consequently, to muscle hypertrophy.

Types of muscle hypertrophy

Myofibrillar

Imagine myofibrillar hypertrophy as the construction of a building. The bricks represent sarcomeres, the basic units of muscle structure. By adding more bricks (sarcomeres) in parallel, the building (the muscle fiber) becomes wider and stronger. This is similar to what happens when we lift weights and our muscle fibers become thicker. On the other hand, adding bricks in series would be like building more floors in the building, which would increase its height but not necessarily its width. However, in the context of muscle hypertrophy, growth in parallel is the predominant mechanism.

Sarcoplasmic

Sarcoplasmic hypertrophy involves not only an increase in cell size, but also changes in the biochemical composition of the muscle. A larger sarcoplasmic volume provides a larger physical space for the location of mitochondria, which may improve the oxidative capacity of the muscle and increase resistance to fatigue. Furthermore, the increase in glycogen content may provide an additional energy source for high-intensity exercise. It has been proposed that sarcoplasmic hypertrophy could play a crucial role in the early stages of muscle growth. By increasing cell volume, space is created for the addition of new myofibrils and the proliferation of satellite cells, the progenitor cells of the muscle, is facilitated. Once a certain threshold of sarcoplasmic growth has been reached, satellite cells can fuse with existing muscle fibers, donating new nuclei and allowing for increased synthesis of contractile proteins.

Connective tissue

Connective tissue hypertrophy is not an isolated phenomenon, but is closely linked to muscle remodeling processes. The extracellular matrix, in addition to providing structural support, acts as a microenvironment that influences muscle cell proliferation, differentiation, and function. Connective tissue cells, such as fibroblasts, interact with muscle fibers through cell adhesion molecules and growth factors, thereby regulating tissue homeostasis. During muscle hypertrophy, a complex interaction between muscle cells and connective tissue occurs. The increased mechanical demand on the muscle stimulates fibroblast proliferation and the synthesis of extracellular matrix proteins, resulting in a thickening of the connective tissue layers. This adaptive response seeks to strengthen the muscle structure and prevent injury.

Hormones

Hormones are chemical messengers that circulate in the bloodstream and influence various bodily functions. Anabolic hormones, such as testosterone, play a crucial role in muscle growth by promoting protein synthesis, the process of creating new muscle tissue.

Insulin-like growth factor 1

The pituitary gland, a small gland located in the brain, produces growth hormone (GH). This hormone is like a superhero for our muscles, as it helps repair them and grow after exercise. When we exercise intensely, our body produces a substance called lactate, which acts as a signal for the pituitary gland to release more GH. So training hard is like giving our growth hormone a boost!

Growth hormone (GH) acts as a potent modulator of metabolism, exerting both catabolic and anabolic effects. On the one hand, it stimulates lipolysis, i.e. the breakdown of fats, thus providing an alternative source of energy for the muscle. On the other hand, GH promotes protein synthesis, especially collagen, which contributes to the growth and repair of tissues, including muscle connective tissue. Although GH does not act directly on muscle contractile proteins, its effect on the extracellular matrix is essential for muscle growth and strength.

The benefits of GH for increasing muscle mass have been widely studied, especially in animal models. However, the results in humans are more complex and often contradictory. While GH undoubtedly stimulates the production of IGF-1, a potent promoter of muscle growth, its direct effect on protein synthesis in human muscles is still not completely clear. The lack of longitudinal studies in humans and individual differences in response to GH make it difficult to draw definitive conclusions.

The hormone hypothesis

The role of hormones in muscle hypertrophy has been the subject of intense debate in the scientific community. While it is widely accepted that hormones such as testosterone and insulin-like growth factor-1 (IGF-1) play a role in regulating muscle growth, their relative importance and the precise mechanisms by which they exert their effects remain a matter of research.

The hormonal hypothesis postulates that increases in circulating levels of these hormones in response to exercise are essential to stimulate muscle protein synthesis and, therefore, hypertrophy. However, this perspective has been challenged by studies suggesting that mechanical stress-induced activation of intracellular signaling pathways is the primary stimulus for muscle growth. These researchers argue that while hormones may potentiate the effects of training, they are not strictly necessary for hypertrophy.

The experimental evidence in this field is complex and often contradictory. Some studies have shown a positive correlation between hormone levels and muscle mass gains, while others have found no such association. Furthermore, the influence of individual factors, such as genetics, age and nutritional status, can moderate the hormonal response to exercise and consequently affect muscle growth.

Exercise-induced muscle hypertrophy

Schoenfeld proposed three key mechanisms for muscle hypertrophy: mechanical tension, muscle damage, and metabolic stress. Although these mechanisms have been widely studied, their relative contribution remains debated. It is important to remember that these models are simplifications of complex biological processes and do not accurately predict muscle growth in each individual. Imagine your muscle as a bank account. When you deposit more protein (synthesis) than you withdraw (breakdown), your account grows (hypertrophy). Stimuli such as weight training are like large deposits that make your muscle grow. If you withdraw more than you deposit, your muscle shrinks.

Mechanical stress

The extracellular matrix, a network of proteins and molecules surrounding muscle cells, plays a crucial role in transducing mechanical signals and regulating muscle growth. Forces applied to the muscle are not only transmitted through sarcomeres and costameres, but also interact with the extracellular matrix, generating a series of mechanical signals that influence muscle cell behavior.

The stiffness, viscosity, and composition of the extracellular matrix can modulate the response of muscle cells to mechanical stress. In addition, the extracellular matrix contains a variety of signaling molecules that can interact with cell surface receptors, amplifying mechanical signals and promoting muscle growth.

Imagine that mechanosensors are the alarm sensors of a building. When an alarm is triggered (muscle tension), a series of coordinated actions (myogenic pathways) are initiated to repair the damage (catabolism) and strengthen the structure of the building (anabolism). In the case of muscle, this repair and strengthening process leads to muscle growth.

Primary anabolic signaling pathways

The mechanical stress generated during weightlifting induces a series of intracellular events that culminate in the activation of anabolic signaling pathways. Mechanosensors located in the cell membrane and cytoskeleton detect the stress and transmit the signal to the interior of the cell. Through a complex network of molecular interactions, transcription factors are activated that promote the expression of genes related to muscle protein synthesis, such as growth factors and myokines.

PI3K/Akt y mTOR

The PI3K/Akt/mTOR pathway is a central signaling cascade in the regulation of cell growth and survival, including muscle hypertrophy. Activation of PI3K by various stimuli, such as growth factors, leads to phosphorylation and activation of Akt. In turn, Akt phosphorylates and activates mTOR, a master regulator of cell growth. mTOR promotes protein synthesis through activation of the mTORC1 pathway, which stimulates the formation of new ribosomes and mRNA translation, processes essential for muscle growth.

Mitogen-activated protein kinase

Mitogen-activated protein kinase (MAPK) is a key player in muscle growth. When we exercise, MAPK is activated and triggers a series of reactions that stimulate the production of new muscle proteins, which in turn increases the size of our muscles.

Calcium-regulated pathways

Calcineurin, a calcium-activated enzyme, influences muscle hypertrophy. Although research results are mixed, its role in regulating muscle mass is clear. In addition, other calcium-dependent enzymes may also be involved.

Muscle growth is like a secret message that is sent to our cells. When we lift weights, we send a signal to the muscle cells, telling them that they need to grow. This signal, like a letter, travels inside the cell and activates a series of processes that cause the cell to produce more proteins to become bigger. Although the details of this process are complex, the important thing to understand is that exercise is the message that starts it all.

Muscle damage

Schoenfeld subsequently questioned some of the central ideas about muscle damage, and new research has since continued to challenge this hypothesis.

What is muscle damage?

The work of Schoenfeld and other researchers has shown that muscle damage is a normal physiological process in response to strength training. Understanding the mechanisms underlying muscle damage is critical to designing more effective training programs and minimizing injury risk.

By performing eccentric exercises, such as negative reps, a greater degree of muscle damage can be induced and therefore stimulate a greater adaptive response. However, it is important to note that excessive muscle damage can delay recovery and increase the risk of injury. Therefore, it is crucial to find a balance between stimulus and stress to optimize training results.

The concept of the "repeated bout effect" suggests that gradual progression of training load and volume is critical to maximizing long-term results. By gradually increasing training intensity and volume, the muscle is allowed to adapt and become more resistant to damage.

In conclusion, muscle damage is a natural and necessary process for muscle growth. By understanding the mechanisms underlying muscle damage and applying the principles of strength training, we can design personalized and effective training programs to achieve our fitness goals.

While strength training can cause muscle damage, this damage isn't necessarily a bad thing. In fact, the process of muscle repair and regeneration after a training session is thought to be what stimulates muscle growth. However, the relationship between muscle damage and hypertrophy is complex and still not fully understood.

Human evidence analyzing muscle damage and hypertrophy

Despite what many believe, the relationship between muscle damage and muscle growth is not as clear-cut as it seems. Some studies show that muscle growth can occur without a lot of damage, while others suggest that too much damage could be counterproductive. Even techniques like BFR show that muscle can be built with less damage. In short, while muscle damage plays a role, it is not the only determining factor for muscle growth.

Metabolic stress

We’ve all experienced that “pumped” feeling in the gym, that muscular fullness that makes us feel stronger. But what’s behind that feeling? Metabolic stress is the scientific term that describes the physiological changes that occur in our muscles during strength training. The buildup of metabolites like lactate and the decrease in intracellular pH are signals our body sends to indicate that we’re working our muscles to the limit. Although lactate has traditionally been considered a waste product, there is growing evidence to suggest that this metabolite may play an important role in stimulating muscle growth.

Blood flow restriction (BFR) training is an innovative technique that takes advantage of metabolic stress to maximize muscle growth. By limiting blood flow, lactic acid and other metabolites build up in the muscle, creating an environment that favors hypertrophy. This training modality allows for similar results to heavier loads, but with a lower risk of injury. That's why more and more people are incorporating BFR into their training routines.

Cell swelling

Cell swelling, a phenomenon induced by intense exercise, plays a crucial role in muscle hypertrophy. This increase in cell volume, attributable to the accumulation of metabolites and water influx, triggers a cascade of molecular events that promote muscle growth. Cell swelling is postulated to activate anabolic signaling pathways, such as mTOR, thus stimulating protein synthesis and muscle hypertrophy. Furthermore, cell swelling could act as a stress signal, inducing the expression of genes related to muscle repair and growth. Cotamers, stretch-sensitive protein structures, could act as sensors of cell swelling, amplifying anabolic signals.

How can you apply this information?

We understand that all this information about cellular mechanisms can sound a little overwhelming. The important thing to remember is that while theory is interesting, practice is what really matters. To gain muscle, you need to lift weights with sufficient intensity and frequency. This means gradually increasing the weight you lift and making sure that each workout is challenging enough.

There is no magic formula for muscle growth, but there are many resources and trainers that can help you find the training program that is best for you.

Muscle hypertrophy is the result of proper stimulation. While the underlying physiological mechanisms are complex, the foundation of any effective training program is lifting weights regularly and progressively. Follow these 4 principles to optimize your results:

Train to the limit: Perform few repetitions with a lot of weight, occasionally reaching muscle failure.
Train a variety of rep ranges and intensities: reps from 4 to 25 with intensities ranging from 30 to 85% of 1RM.
Build volume: 10 sets per muscle group weekly is a good starting point for most.
Customize your workout: Choose exercises that strengthen your weaker muscles and allow you to move freely.
Want to maximize your muscle gains? Include at least two training sessions per muscle group in your weekly routine!