What causes muscle growth?

If you enjoy this article, you will like my second book (see on Amazon).

For many centuries, we have known that lifting weights increases strength, as well as muscle mass. Thousands of years ago, Milo of Croton developed tremendous strength for Olympic wrestling by lifting a calf on his shoulders each day, growing bigger and stronger as it grew heavier.

More recently, in the late 1800s, strongmen like Eugen Sandow included posing routines at the end of their weight lifting performances, to show off the muscular development they had achieved through training.

In other words, we figured out a long time ago that lifting progressively heavier weights was necessary to keep increasing strength. However, it was not until recently that researchers began studying strength training, and applied the scientific method to identify exactly what causes muscle growth, by exploring the mechanisms and processes through which lifting weights causes hypertrophy.

This research is an important resource for our understanding of strength training. By learning about the mechanisms and processes by which strength training causes muscle growth, we can structure our training programs to maximize the results we want to achieve.

This is the second article in a series about muscle growth. Here is part one.

What are the mechanisms and processes that lead to muscular hypertrophy?

There are three main phases in the process through which strength training causes muscle growth. Each of these phases has been examined by researchers, although some have been given more attention than others.

Firstly, there is an initial stimulus, often called the primary mechanism. Since muscle growth happens primarily through an increase in the size of individual muscle fibers, this must be detected by receptors inside the muscle cells. Secondly, there are molecular signaling events inside the muscle. These last several hours, and result from the initial stimulus. Thirdly, there is a temporary increase in the rate of muscle protein synthesis, which is triggered by the molecular signaling events. This is what leads to increases in overall muscle size, which can then be measured in various ways.

#1. Initial stimulus

Researchers have identified three primary mechanisms that might stimulate muscle growth: (1) mechanical tension, (2) metabolic stress, and (3) muscle damage. These mechanisms are environmental conditions that can be detected by single muscle fibers, which then stimulate the molecular signaling events that increase muscle protein synthesis rates, and subsequently cause the accumulation of protein inside individual muscle fibers.

Currently, we have a fairly clear model for how mechanical tension triggers muscle growth, although the location and identity of the mechanoreceptors within the muscle fibers are still unknown. In contrast, the roles played by muscle damage and metabolic stress are far less clear, mainly because of the problems inherent in examining these factors.

The main difficulty faced by researchers when trying to understand the independent effects of mechanical tension, muscle damage, and metabolic stress is that it is very difficult to stimulate a muscle with either muscle damage or metabolic stress while not providing the mechanical tension stimulus at the same time.

Some researchers have also suggested that muscle fiber activation, resulting from motor unit recruitment, is a primary mechanism through which muscle growth is stimulated. But this cannot be the case, because full motor unit recruitment is approached in high-velocity muscle contractions, which cause little muscle growth.

Moreover, when muscle activation is maintained constant at high levels, increasing the velocity of a contraction reduces hypertrophy. This seems to happen because faster contraction velocities reduce the mechanical tension produced by each muscle fiber, and therefore the amount of mechanical loading detected by its mechanoreceptors.

#2. Molecular signaling

Researchers have revealed a complex array of signaling pathways that are activated in response to strength training workouts, and which seem to be involved in elevating muscle protein synthesis, and causing the accumulation of protein inside muscle fibers.

Most famous of these molecular pathways is the mTOR signaling pathway, which has a downstream target (p70S6K) that has been closely related to long-term increases in muscle size, in both animals and humans. Moreover, many training variables that have been linked to greater muscle growth also display elevated p70S6K signaling, including workout volume.

However, some training variables that do not appear to enhance muscle growth also display elevated p70S6K signaling, including eccentric (compared to concentric) contractions. This may imply that mTOR signaling is also involved in other processes, such as the repair of muscle damage, as lengthening contractions cause more muscle damage than shortening contractions.

In fact, there are even situations in which mTOR signaling can be stimulated and phosphorylated p70S6K increased, and yet muscle protein synthesis rates are not elevated. This has been reported in cases of overtraining, which can cause muscle loss, and where oxidative stress seems to inhibit muscle protein synthesis from being increased.

The results of such experiments provide a cautionary note that we should not assume that a greater increase in mTOR signaling will *always* cause a greater increase in muscle protein synthesis rates, and a subsequent long-term increase in muscle size.

#3. Muscle protein synthesis

Until very recently, researchers had been unable to link the increases in muscle protein synthesis rates after a workout to the long-term gains in muscle size after a strength training program comprising a sequence of that type of workout, although they often observed transitory increases after a single workout.

Even though the protein content of a muscle fiber is determined by the ongoing balance of muscle protein synthesis and muscle protein breakdown rates, this was still frustrating, because there was good evidence to suggest that it was the increase in muscle protein synthesis rate that was responsible for the change in muscle size over time.

Consequently, it was a real breakthrough when a research group identified very recently that elevations in muscle (myofibrillar) protein synthesis could be related to long-term gains in muscle size after taking away the uplift in muscle protein synthesis rates required to repair damaged muscle tissue.

This discovery was important, not only because it confirmed the central role of increasing muscle protein synthesis rates for causing hypertrophy, but also because it hinted that while muscle damage repair and muscle growth are very similar processes, repairing muscle damage probably does not enhance increases in muscle size.

Additionally, the study also suggests that the popular study design in which post-workout elevations in muscle protein synthesis are measured may not be as useful as we had previously hoped. Since muscle protein synthesis rates are increased both in order to repair muscle damage (which does not enhance hypertrophy) and also to increase muscle fiber protein content (which causes hypertrophy), such studies may lead us to conclude *incorrectly* that more muscle-damaging workouts lead to greater muscle growth.

Therefore, as with molecular signaling, we should be cautious about how we interpret the findings of studies exploring changes in muscle protein synthesis after a workout, since such changes could easily reflect the repair of muscle damage, rather than the growth of muscle tissue.

What do we know about mechanical tension?


There are three important areas to address when thinking about the role of mechanical tension in muscle growth: (1) the nature of active and passive mechanical tension, (2) the role of external resistance, and (3) the effects of fatigue.

#1. Active and passive mechanical tension

Muscles can experience mechanical tension either when they are contracting actively, or when they are passively stretched. When they are actively contracting, they can produce force either while shortening, lengthening, or remaining at a constant length (isometric). In all cases, the amount of mechanical tension has been related to the subsequent change in muscle size, thereby confirming the key role of this mechanism in hypertrophy.

While we are most accustomed to muscle growth happening after strength training using active muscle contractions, hypertrophy has also been reported after passive stretching of inactive muscle, in both humans and animals, and very likely involves somewhat similar molecular signaling through the mTOR pathway.

Interestingly, however, it seems likely that muscle fibers can detect the difference between mechanical tension provided by active contractions and by passive loading.

This is reflected in the nature of the molecular signaling through the mTOR pathway, and also in the long-term adaptations to strength training, which are often greater after combining both active and passive loading, even when muscle forces are equated. Practically speaking, this suggests that muscular contractions and stretching provide independent, and additive stimuli that lead to muscle growth.

#2. The role of external resistance

The way in which mechanical tension causes muscle growth is frequently misunderstood, because we tend to think of the external resistance as being the mechanical stimulus. While this is appropriate when thinking about passive stretching of muscle tissue, it is not valid when thinking about strength training in which active muscle contractions are involved.

The mechanical tension signal that leads to hypertrophy is detected by single fibers and not by the muscle as a whole, by mechanoreceptors that are probably located on membrane of each muscle cell. This is an important factor, because it means that we need to define the mechanical tension stimulus in related to the forces experienced by each individual muscle fiber, and not by the whole muscle.

In this respect, there are two key points.

Firstly, in an active muscle contraction, the tensile force sensed by a muscle fiber is essentially the force it produces itself. Even so, in the absence of fatigue, it is the external resistance that determines the speed at which each fiber can contract. Since slower contraction velocities allow more actin-myosin crossbridges to form inside a fiber, larger external resistances thereby increase the tension that each fiber produces, because the number of attached actin-myosin crossbridges determines the force produced by a fiber.

Indeed, while the resistance must be external to the muscle, it can be internal to the body, such as when contracting the agonist and antagonist muscles simultaneously.

Secondly, muscle fibers interact with one another, bulging outwards in the middle of the sarcomere and exerting force laterally, and the whole muscle bends and changes shape during a contraction. This means that a muscle contraction exposes its fibers to a variety of external constraints. This leads to different fiber shortening velocities, mechanical tension, and length changes, and this affects the fibers of some regions more than others. This is probably why muscles do not adapt uniformly after strength training, but some regions increase fiber diameter and/or length more than others.

#3. The effects of fatigue

When doing multiple, repeated muscle contractions, fatigue develops.

This means that the muscle fibers governed by the working motor units become unable to produce the required force, and this causes higher threshold motor units to be recruited, and their associated muscle fibers are then activated.

In addition, the fatigue causes the working muscle fibers to reduce their contraction velocity over the set. This reduction in contraction velocity is closely linked to the amount of metabolic stress in the muscle.

Consequently, during fatiguing sets with any load, high-threshold motor units that grow after strength training are activated, and their muscle fibers contract at a slow speed. Since the muscle fibers shorten at a slow speed, a large number of attached actin-myosin crossbridges are formed, and this produces mechanical tension on the fiber, which stimulates it to grow.

What do we know about metabolic stress?

Training with heavy or light loads produces similar muscle growth (so long as sets are performed to failure), and light load training with blood flow restriction also produces similar gains in muscle size to heavy load training.

Such observations have sometimes been used to support the role of metabolic stress in hypertrophy. However, as noted above, there is a very simple explanation for how fatigue leads to increased mechanical tension on the muscle fibers of high-threshold motor units, stimulating them to grow.

In fact, because of this effect of fatigue on mechanical tension, it is extremely difficult to explore the independent effects of metabolic stress on muscle growth.

To get around the problem, some researchers have tested the long-term effects of periodically applying blood flow restriction to a muscle without any simultaneous muscular contractions, either as a standalone intervention in rodents, or immediately after a workout in humans. However, the findings of this research have been conflicting. At present, it therefore seems likely that the effects of metabolic stress are *largely* mediated by fatigue, insofar as fatigue enhances muscle growth by increasing mechanical loading.

What do we know about muscle damage?

It is often thought that eccentric training causes greater muscle growth than concentric training. Similarly, training at long muscle lengths (involving stretch) often (but not always) causes more muscle growth than training at short muscle lengths.

Since both eccentric contractions and training at long muscle lengths cause more muscle damage than concentric contractions and training at short muscle lengths, these observations have been used to support the role of muscle damage in hypertrophy.

While eccentrics do cause more muscle damage than concentrics, this does not translate to greater hypertrophy in rodent models. And in humans, suppressing the muscle-damaging effects of eccentric contractions seems to have little impact on muscle growth, and if eccentrics do cause more muscle growth than concentrics, then the effect is quite small. The differences between eccentric and concentric training observed in some studies may be related to the measurement methods used: new research has shown that eccentrics cause larger increases in muscle fiber length, while concentrics cause greater gains in fiber diameter, while overall hypertrophy is similar.

Perhaps more importantly, carefully-controlled rodent research has shown that the varying effects of different types of muscle contractions (concentric, eccentric, and isometric) on muscle growth are explained almost entirely by the amount of mechanical tension involved. In other words, while some eccentric training programs might indeed produce greater muscle growth than a comparable concentric training program, the effect is most likely mediated by the higher level of mechanical tension and/or work done that can be achieved with lengthening contractions.

Similarly, the role of increased muscle length in stimulating muscle growth is unclear. While passive stretching can cause muscle growth in both humans and animals, it is unclear whether this happens because of a tension-sensing mechanism or a damage-sensing mechanism. Given that passive stretching rarely causes muscle soreness (unlike strength training), it seems plausible that the mechanism involves sensing tension rather than damage.

Increasingly, therefore, researchers are suggesting that the repair of muscle damage is a separate process from muscle growth. Indeed, studies have shown that elevations in muscle protein synthesis are only related to long-term gains in muscle size after taking away the uplift in muscle protein synthesis rates required to repair damaged muscle tissue.

However, all of the above research involved drawing conclusions from strength training workouts in which both mechanical tension and muscle damage could have stimulated hypertrophy. As with metabolic stress, it is very difficult to explore the independent effects of mechanical tension and muscle damage on muscle growth.

To get around the problem, some researchers have tested the long-term effects of other types of mechanical loading, such as mechanical compression, on muscle growth. Mechanical compression produces similar muscle damage as mechanical tension, even causing split muscle fibers in some cases, and all types of muscle damage seem to be repaired in much the same way.

If the process of muscle repair after compressive loading were to trigger hypertrophy, then this would be good evidence that it is a primary mechanism that leads to muscle growth. So far, however, the research suggests that it does not, and may in fact cause the loss of some muscle fibers as a result of the damage. Other studies have also shown that excessive muscle damage is likely responsible for both overreaching and muscle loss, when delivered alongside mechanical tension, both in humans and animals.

At present, it therefore seems most likely that that any apparent effects of muscle damage are *largely* a function of the muscle-damaging workout involving either (1) greater mechanical loading, or (2) the sensing of stretch.

What is the takeaway?

There are three main phases in the process through which strength training causes muscle growth, which have been examined by researchers: (1) the primary mechanism, (2) molecular signaling events, and (3) changes in muscle protein synthesis rates, which are responsible for the long-term accumulation of protein inside muscle fibers, and an increase in muscle size.

Currently, we have a clear model for how the primary mechanism of mechanical tension can produce muscle growth, and it is determined by the tension produced and detected by each muscle fiber. This tension is produced by the number of attached actin-myosin crossbridges, which is greater at slower fiber contraction velocities. Fiber contraction velocity (and therefore the amount of mechanical tension) can be reduced by either a higher external resistance or more fatigue.

In contrast, the roles of metabolic stress and muscle damage are much less clear, mainly because they are difficult to investigate independently from mechanical tension. Currently, the role of metabolic stress can be explained well by the effects of fatigue on increasing mechanical tension. Similarly, any potential effects of muscle damage that might arise when eccentric training or training at long muscle lengths can be just as easily explained by greater mechanical loading or the sensing of stretch.

If you enjoyed this article, you will like my second book (see on Amazon).



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