Skeletal muscles are the main tissues that support the motor functions of the human body, and their development and characteristics are determined by the interaction of genetic and environmental factors. Recent genetic research has revealed the existence of genes that affect skeletal muscle growth and performance. This article focuses on genetic factors related to skeletal muscle development and provides scientifically based information.
Basic structure and functions of skeletal muscles
What is skeletal muscle?
Skeletal muscles are made up of bundles of long, thin cells called muscle fibers, which contract using proteins called actin and myosin. Their main functions are:
Control of movement: Moving joints and enabling walking and lifting.
Maintaining posture: Supports standing or sitting for long periods of time.
Energy metabolism: ATP is produced using glucose and lipids.
Thermoregulation: Produces heat through muscle contraction to maintain body temperature.
Skeletal muscle development and genetic factors
How genes affect muscle development
Genes influence muscle fiber type, ease of muscle hypertrophy, endurance, etc. Previous research has suggested that certain genes are involved in skeletal muscle growth and performance improvement.
1. ACTN3 gene and fast-twitch muscle fibers
The ACTN3 (α-actinin-3) gene is one of the main genes involved in the function of fast-twitch muscle fibers (type II fibers). When this gene is normally expressed, the contractile force of fast-twitch muscle fibers increases, which is considered to be advantageous for power sports such as sprinting and weightlifting.
However, some people have a mutation in the ACTN3 gene (R577X mutation) that reduces the function of fast-twitch muscle fibers, suggesting that these individuals may have a muscle composition that is better for endurance but less able to exert explosive power.
The myostatin (MSTN) gene encodes a protein that inhibits muscle growth. When myostatin activity is reduced, muscle growth is promoted, so it is known that individuals with genetically weak function of this gene are more likely to develop muscles.
Animal studies have shown that suppressing myostatin significantly increases muscle mass, and mutations in the myostatin gene may also affect muscle size in humans.
The PGC-1α (PPARGC1A) gene promotes mitochondrial production and oxidative metabolism, contributing to improved endurance. When this gene is activated, endurance muscle activity improves and energy-efficient muscles are formed.
Endurance athletes tend to have higher expression of PGC-1α, and it has also been reported that aerobic exercise increases the activity of this gene.
Although genes influence muscle development, environmental factors are also important: training, nutrition, and hormone balance can alter gene expression and thus affect skeletal muscle growth.
1. Exercise training and gene expression
Resistance training (strength training) affects the expression of ACTN3 and MSTN and promotes muscle hypertrophy.
Endurance exercise (running and cycling) increases PGC-1α activity, leading to an increase in mitochondria and improved muscle endurance.
2. Nutrition and gene expression
Protein intake and certain amino acids (such as leucine) activate the mTOR signaling pathway and promote muscle protein synthesis, and supplements such as creatine and beta-alanine may also contribute to muscle growth.
3. Hormonal influences
Testosterone promotes muscle protein synthesis and accelerates muscle hypertrophy.
Cortisol promotes muscle breakdown, and excessive stress or exercise can put you at risk of losing muscle mass.
4. FOXO3 gene and suppression of muscle aging
Aging-related muscle loss (sarcopenia) leads to decreased physical activity and reduced quality of life (QOL) in the elderly. The FOXO3 gene has been reported to be involved in cellular stress response and maintaining mitochondrial function, and to play a role in suppressing the progression of aging.
It has been shown that decreased FOXO3 activity reduces autophagy (the cell’s self-repair function) and accelerates muscle atrophy. Conversely, increasing FOXO3 activity through moderate exercise and nutritional management may prevent muscle loss due to aging.
Interleukin-6 (IL-6) is a cytokine that acts in the immune system and is involved in recovery after muscle injury. IL-6 plays a role in regulating the inflammatory response and promoting muscle repair.
Research has shown that the amount of IL-6 secreted varies depending on an individual’s genetic background and also affects the speed of muscle recovery. Moderate expression of IL-6 is beneficial for muscle repair, while excessive inflammation can actually cause muscle breakdown.
Genetic polymorphisms and individual differences in training
Specific genetic polymorphisms (SNPs: Single Nucleotide Polymorphisms) are involved in the development of skeletal muscles and are a factor in individual differences in the ability to adapt to training.
1. The ACE gene and endurance vs. strength
The angiotensin-converting enzyme (ACE) gene affects blood pressure regulation and muscle performance. There are two polymorphisms in this gene, “type I (insertion type)” and “type D (deletion type)”, each of which has different characteristics.
Type I (insertion type) : Common in endurance athletes, associated with improved cardiopulmonary function and enhanced oxygen supply capacity.
Type D (deficiency type) : Common in strength and power athletes, adapted to high-intensity performance in a short period of time.
The AMPD1 gene encodes an enzyme involved in the supply of energy to muscles. It has been reported that people with certain mutations in this gene are more susceptible to muscle fatigue.
Athletes with AMPD1 mutations tend to recover slower after high intensity exercise but may be better suited to endurance exercise and may benefit from certain types of training.
The effects of genes are not fixed but can be modulated by environmental factors (diet, exercise, stress, etc.) This phenomenon is called “epigenetics.”
1. DNA methylation and muscle development
DNA methylation is one of the important mechanisms regulating gene expression. It has been reported that resistance training and aerobic exercise change the methylation patterns of genes involved in muscle growth.
For example, it is known that continued resistance training reduces DNA methylation and activates expression of genes related to muscle hypertrophy (e.g., IGF-1, MyoD).
Histone modification is a process that regulates how DNA is packed and which genes are transcribed. Training type and frequency can alter histone acetylation and methylation patterns, influencing muscle adaptation.
In particular, endurance training has been suggested to increase histone acetylation and enhance the expression of genes that promote oxidative metabolism (e.g., PGC-1α).
Performance improvement strategies using genetic information
Understanding and utilizing your genetic information can lead to more effective training and dietary plans.
1. Optimizing training through genetic testing
In recent years, genetic testing that analyzes an individual’s genetic information has become widespread, and by examining genes such as ACTN3, ACE, and PGC-1α, it is now possible to select a training method that is best suited to you.
Fast-twitch muscle type (ACTN3 R type) → Emphasis on power training
Endurance type (high expression of PGC-1α) → mainly aerobic exercise
Easy to build muscle (MSTN mutation) → Adopt a high-protein diet
2. Personalized Nutrition
Tailoring your nutrition to your genetics will help maximize muscle development and performance.
Muscle hypertrophy (low MSTN expression) → high protein, high calorie diet
Endurance type (high expression of PGC-1α) → high carbohydrate and antioxidant intake
Delayed recovery (AMPD1 mutation) → Support with creatine and BCAA intake
3. MicroRNAs (miRNAs) and skeletal muscle regulation
In recent years, it has become clear that microRNAs (miRNAs) , short RNA molecules that control gene expression and regulate protein synthesis and cell signaling, play important roles in skeletal muscle growth and adaptation.
The role of miR-1 and miR-133
miR-1 and miR-133 are representative miRNAs involved in skeletal muscle development and adaptation.
miR-1 promotes muscle cell differentiation and supports myogenesis.
miR-133 promotes muscle hypertrophy and contributes to muscle fiber growth.
It has been suggested that changes in exercise and nutritional intake alter the expression of these miRNAs, promoting muscle adaptation.
4. mTOR signaling pathway and muscle protein synthesis
Mechanistic target of rapamycin (mTOR) is one of the central signaling pathways that regulates cell growth and metabolism and is involved in promoting muscle protein synthesis.
mTOR Activation and Muscle Growth
Resistance training and protein intake (especially leucine) activate the mTOR pathway and promote muscle protein synthesis.
Insulin and insulin-like growth factor 1 (IGF-1) also support muscle hypertrophy through activation of mTOR.
In order to maximize the function of mTOR, it is important to consume proper nutrition after exercise, and in particular, proteins containing leucine (such as whey protein) are recommended.
The female hormone estrogen plays an important role in the maintenance and regeneration of skeletal muscles. It has been reported that estrogen receptors (ERβ) are present in muscle fibers and muscle stem cells and regulate muscle growth and repair.
Estrogen’s effects on muscles
Promotes repair after muscle injury.
Maintains mitochondrial function and supports energy metabolism.
Reduces oxidative stress and inhibits the aging of muscle cells.
As estrogen secretion decreases with age, the risk of muscle loss (sarcopenia) increases, so maintaining hormone balance is important.
6. Muscle satellite cells and regenerative capacity
Muscle satellite cells (MSCs) are stem cells that play an important role in muscle repair and regeneration after muscle injury. These cells normally reside outside muscle fibers and become activated upon muscle injury to generate new muscle cells.
Satellite cell activation and genetic factors
The Pax7 gene is a key factor regulating the self-renewal and differentiation of muscle satellite cells.
The Notch signaling pathway regulates the activation of muscle satellite cells and promotes timely muscle regeneration.
Proper nutrition and exercise are important for maintaining satellite cell activity and enhancing muscle regeneration capacity.
7. The relationship between sleep and muscle development
Sleep also plays an important role in muscle development . Growth hormone (GH) is secreted during sleep, promoting muscle protein synthesis and muscle repair.
The relationship between genes and sleep
The CLOCK gene regulates circadian rhythms (body clocks) and affects sleep quality and hormone secretion.
Sleep deprivation reduces activity of the mTOR pathway and inhibits muscle protein synthesis.
Improving your sleep habits is also important for muscle development, as getting quality sleep maximises muscle repair and growth.
Potential for using genetic information to improve performance
9. Gene editing technology and the future of muscle development
Recent gene editing techniques, such as CRISPR-Cas9 , have the potential to improve muscle growth and function. Gene editing can be used to suppress genes that inhibit muscle development (e.g., MSTN ), which is expected to increase muscle mass and strength.
The potential of MSTN gene editing
Myostatin (MSTN) plays a role in suppressing excessive muscle growth.
Inhibiting MSTN can promote muscle hypertrophy and improve muscle strength.
Animal experiments using CRISPR-Cas9 technology have shown increased muscle mass and improved athletic performance.
Currently, this technology is expected to be primarily applied to the treatment of genetic diseases such as muscular dystrophy, but in the future it may also be used in the sports field.
As the influence of genes on sports performance becomes more clear, a new field called sports genomics is developing.
Risks and ethical issues of gene doping
There are concerns about “gene doping” using gene editing technology. The World Anti-Doping Agency (WADA) prohibits the artificial manipulation of certain genes and is strengthening its monitoring of gene doping.
Enhancement of EPO (erythropoietin) gene: Improves oxygen transport capacity and increases endurance.
Inhibition of MSTN: Promotes muscle hypertrophy and provides an advantage in power sports.
These technologies pose the risk of undermining the fairness of sports, and it is expected that regulatory and ethical debates will continue in the future.
References : WADA, “Gene Doping”
11. Genetic counseling and personalized training
In recent years, the importance of individual optimization training utilizing genetic counseling has increased.
Genetics-Informed Training Plans
By utilizing genetic information, it is possible to design training programs tailored to individual characteristics.
ACTN3 R type (fast muscle type) → High-intensity training for sprinting and weightlifting
High expression of PGC-1α (endurance type) → Aerobic exercise-centered program
Low expression of MSTN (muscle hypertrophy) → High protein diet and strength training to maximize muscle hypertrophy
Recovery strategies using genetic information
If you have an AMPD1 mutation, recovery is slower, so adequate rest and the intake of BCAAs and creatine are recommended.
If FOXO3 activity is low, supplement with antioxidants (vitamins C and E) to maintain mitochondrial function.
13. The future of genetic testing and challenges to its practical application
Genetic testing has attracted attention as a means of learning about an individual’s physical constitution and athletic aptitude, but scientific challenges remain.
Current Issues\
Genes alone cannot determine ability Athletic ability is determined by the interaction of many genes and environmental factors, so it is difficult to judge ability based on a single gene’s information alone.
Data bias: Most current genetic studies are conducted on Western subjects, and their applicability to Asians needs to be carefully considered.
Privacy Issues If genetic information is not properly managed, there is a risk that an individual’s genetic characteristics may be misused.
Future outlook
By utilizing AI and big data , the accuracy of individually optimized training is improved.
Advances in epigenetic research have made it possible to regulate gene expression through environmental factors.
Collaboration with the medical sector has led to the development of an integrated approach to sports and health management.
In the latest research, the development of genetic analysis technology has made it possible to analyze the muscle development characteristics of individuals in detail. More efficient muscle development can be expected by individualizing training plans and nutritional strategies based on genes such as ACTN3, MSTN, PGC-1α, and FOXO3.
By understanding the genetic background of muscle development and taking into account interactions with environmental factors, we can aim to maximize performance improvement.
Summary
In this article, we have provided a detailed explanation of the genetic factors that influence skeletal muscle development. Genes such as ACTN3, MSTN, PGC-1α, and FOXO3 are involved in the type, growth, and recovery ability of muscle fibers, and their interaction with environmental factors determines muscle development. In addition, advances in epigenetics and gene editing technology are expanding the possibilities for optimizing muscle adaptation. In the future, individual optimization training using genetic information will become commonplace, leading to more efficient muscle strength improvement.
