How do muscles grow?
Young sub Kwon, M.S. and Len Kravitz, Ph.D.

Article Reviewed:
Charge, S. B. P., and Rudnicki, M.A. (2004). Cellular and molecular regulation of muscle regeneration. Physiological Reviews, Volume 84, 209-238.

Introduction
Personal trainers and fitness professionals often spend countless hours reading articles and research on new training programs and exercise ideas for developing muscular fitness. However, largely because of its physiological complexity, few fitness professionals are as well informed in how muscles actually adapt and grow to the progressively increasing overload demands of exercise. In fact, skeletal muscle is the most adaptable tissue in the human body and muscle hypertrophy (increase in size) is a vastly researched topic, yet still considered a fertile area of research. This column will provide a brief update on some of the intriguing cellular changes that occur leading to muscle growth, referred to as the satellite cell theory of hypertrophy.

Trauma to the Muscle: Activating The Satellite Cells
When muscles undergo intense exercise, as from a resistance training bout, there is trauma to the muscle fibers that is referred to as muscle injury or damage in scientific investigations. This disruption to muscle cell organelles activates satellite cells, which are located on the outside of the muscle fibers between the basal lamina (basement membrane) and the plasma membrane (sarcolemma) of muscles fibers to proliferate to the injury site (Charge and Rudnicki 2004). In essence, a biological effort to repair or replace damaged muscle fibers begins with the satellite cells fusing together and to the muscles fibers, often leading to increases in muscle fiber cross-sectional area or hypertrophy. The satellite cells have only one nucleus and can replicate by dividing. As the satellite cells multiply, some remain as organelles on the muscle fiber where as the majority differentiate (the process cells undergo as they mature into normal cells) and fuse to muscle fibers to form new muscle protein stands (or myofibrils) and/or repair damaged fibers. Thus, the muscle cells’ myofibrils will increase in thickness and number. After fusion with the muscle fiber, some satellite cells serve as a source of new nuclei to supplement the growing muscle fiber. With these additional nuclei, the muscle fiber can synthesize more proteins and create more contractile myofilaments, known as actin and myosin, in skeletal muscle cells. It is interesting to note that high numbers of satellite cells are found associated within slow-twitch muscle fibers as compared to fast-twitch muscle fibers within the same muscle, as they are regularly going through cell maintenance repair from daily activities.

Growth factors
Growth factors are hormones or hormone-like compounds that stimulate satellite cells to produce the gains in the muscle fiber size. These growth factors have been shown to affect muscle growth by regulating satellite cell activity. Hepatocyte growth factor (HGF) is a key regulator of satellite cell activity. It has been shown to be the active factor in damaged muscle and may also be responsible for causing satellite cells to migrate to the damaged muscle area (Charge and Rudnicki 2004).
Fibroblast growth factor (FGF) is another important growth factor in muscle repair following exercise. The role of FGF may be in the revascularization (forming new blood capillaries) process during muscle regeneration (Charge and Rudnicki 2004).
A great deal of research has been focused on the role of insulin-like growth factor-I and –II (IGFs) in muscle growth. The IGFs play a primary role in regulating the amount of muscle mass growth, promoting changes occurring in the DNA for protein synthesis, and promoting muscle cell repair.
Insulin also stimulates muscle growth by enhancing protein synthesis and facilitating the entry of glucose into cells. The satellite cells use glucose as a fuel substrate, thus enabling their cell growth activities. And, glucose is also used for intramuscular energy needs.


Growth hormone is also highly recognized for its role in muscle growth. Resistance exercise stimulates the release of growth hormone from the anterior pituitary gland, with released levels being very dependent on exercise intensity. Growth hormone helps to trigger fat metabolism for energy use in the muscle growth process. As well, growth hormone stimulates the uptake and incorporation of amino acids into protein in skeletal muscle.
Lastly, testosterone also affects muscle hypertrophy. This hormone can stimulate growth hormone responses in the pituitary, which enhances cellular amino acid uptake and protein synthesis in skeletal muscle. In addition, testosterone can increase the presence of neurotransmitters at the fiber site, which can help to activate tissue growth. As a steroid hormone, testosterone can interact with nuclear receptors on the DNA, resulting in protein synthesis. Testosterone may also have some type of regulatory effect on satellite cells.

Muscle Growth: The ‘Bigger’ Picture
The previous discussion clearly shows that muscle growth is a complex molecular biology cell process involving the interplay of numerous cellular organelles and growth factors, occurring as a result of resistance exercise. However, for client education some important applications need to be summarized. Muscle growth occurs whenever the rate of muscle protein synthesis is greater than the rate of muscle protein breakdown. Both, the synthesis and breakdown of proteins are controlled by complimentary cellular mechanisms. Resistance exercise can profoundly stimulate muscle cell hypertrophy and the resultant gain in strength. However, the time course for this hypertrophy is relatively slow, generally taking several weeks or months to be apparent (Rasmussen and Phillips, 2003). Interestingly, a single bout of exercise stimulates protein synthesis within 2-4 hours after the workout which may remain elevated for up to 24 hours (Rasmussen and Phillips, 2003). Some specific factors that influence these adaptations are helpful to highlight to your clients.

All studies show that men and women respond to a resistance training stimulus very similarly. However, due to gender differences in body size, body composition and hormone levels, gender will have a varying effect on the extent of hypertrophy one may possibly attain. As well, greater changes in muscle mass will occur in individuals with more muscle mass at the start of a training program.


Aging also mediates cellular changes in muscle decreasing the actual muscle mass. This loss of muscle mass is referred to as sarcopenia. Happily, the detrimental effects of aging on muscle have been shown be restrained or even reversed with regular resistance exercise. Importantly, resistance exercise also improves the connective tissue harness surrounding muscle, thus being most beneficial for injury prevention and in physical rehabilitation therapy.


Heredity differentiates the percentage and amount of the two markedly different fiber types. In humans the cardiovascular-type fibers have at different times been called red, tonic, Type I, slow-twitch (ST), or slow-oxidative (SO) fibers. Contrariwise, the anaerobic-type fibers have been called the white, phasic, Type II, fast-twitch (FT), or fast-glycolytic (FG) fibers. A further subdivision of Type II fibers is the IIa (fast-oxidative-glycolytic) and IIb (fast-glycolytic) fibers. It is worthy of note to mention that the soleus, a muscle involved in standing posture and gait, generally contains 25% to 40% more Type I fibers, while the triceps has 10% to 30% more Type II fibers than the other arm muscles (Foss and Ketyian, 1998). The proportions and types of muscle fibers vary greatly between adults. It is suggested that the new, popular periodization models of exercise training, which include light, moderate and high intensity training phases, satisfactorily overload the different muscle fiber types of the body while also providing sufficient rest for protein synthesis to occur.

Muscle Hypertrophy Summary
Resistance training leads to trauma or injury of the cellular proteins in muscle. This prompts cell-signaling messages to activate satellite cells to begin a cascade of events leading to muscle repair and growth. Several growth factors are involved that regulate the mechanisms of change in protein number and size within the muscle. The adaptation of muscle to the overload stress of resistance exercise begins immediately after each exercise bout, but often takes weeks or months for it to physically manifest itself. The most adaptable tissue in the human body is skeletal muscle, and it is remarkably remodeled after continuous, and carefully designed, resistance exercise training programs.

Additional References:
Foss, M.L. and Keteyian, S.J. (1998). Fox’s Physiological Basis for Exercise and Sport. WCB McGraw-Hill.
Rasmussen, R.B., and Phillips, S.M. (2003). Contractile and Nutritional Regulation of Human Muscle Growth. Exercise and Sport Science Reviews. 31(3):127-131.

Biographies:
Young sub Kwon, MS, CSCS, is a doctoral student in the exercise science program at the University of New Mexico, Albuquerque. He earned his master's degree in exercise physiology in 2001 and has research interests in the field of resistance training and clinical exercise physiology. Before coming to the U.S. he was an exercise specialist in a hospital in Korea.

Len Kravitz, PhD, is the program coordinator of exercise science and a researcher at UNMA, where he won the 2004 Outstanding Teacher of the Year Award. He was also honored with the 1999 Canadian Fitness Professionals International Presenter of the Year Award, and was the first person to win the IDEA Fitness Instructor of the Year Award.