• Introduction
  • The basics of satellite cells
  • Satellite cells and aging
  • Final thoughts
  • Sources
  • Atrophy: a decrease in tissue size.
  • Daughter cells: progeny cells produced after a single cell undergoes cell division.
  • Differentiation: the process in which a stem cell alters from one type to a differentiated one.
  • Cytoplasm: a rich, semifluid material that exists outside of the nucleus and enclosed within the cell membrane of a cell.
  • Hypertrophy: an increase in tissue size.
  • Myoblast: the embryonic precursors of myocytes (muscle cells)
  • Myofibril: a basic rod-like organelle of a muscle cell made up of repeating subunits called sarcomeres. Myofibrils constitute the contractile system, which consists of four complex proteins: myosin, actin, tropomyosin, and troponin.
  • Myonuclear domain theory: each nucleus of a muscle cell controls the functioning of a defined volume of cytoplasm.
  • Proliferation: a rapid reproduction of a cell.
  • Sarcomere: the smallest functional unit of striated muscle tissue.

Introduction

Skeletal muscle is a type of striated muscle tissue which accounts for approximately 40% of adult human body weight. Its main function is to maintain vital functions such as movement, postural support, breathing, and thermogenesis (the process of heat production in organisms). Skeletal muscle tissue is composed of multinucleated contractile muscle cells called myofibers. 

Skeletal muscle cells have a remarkable ability to heal after injury. As a response to tissue damage, skeletal muscles undergo a complex process of degeneration and regeneration that takes place at the tissue, cellular, and molecular levels. This lifelong maintenance of muscle tissue is mediated by satellite cells, (the most abundant skeletal muscle stem cells), which lie in close proximity to the muscle fibers. 

Findings from studies suggest that skeletal muscle satellite cells play an essential part in muscle fiber maintenance, repair, and remodeling. However, understanding the complex cellular and molecular relationship between satellite cells and their dynamic microenvironment remains a substantial challenge.

This post sheds light into the mechanisms of how satellite cells repair muscle tissue after an injury or as a response to training.

The basics of satellite cells

Most cells in the body have only one nucleus, whereas muscle cells have multiple nuclei. According to the myonuclear domain theory, each nucleus of a muscle cell controls the functioning of a defined volume of cytoplasm (a rich, semifluid material that exists outside of the nucleus and enclosed within the cell membrane of a cell). Thus, whenever a muscle grows (hypertrophy) or shrinks (atrophy), the number of myonuclei change accordingly.

A general consensus is that hypertrophy is accompanied by the addition of new nuclei from stem cells (unspecialized cells with the ability to develop into many different cell types) called satellite cells. These unspecialized cells are essential for muscle regeneration and growth due to their ability to replicate (self-renew) and differentiate (a process where unspecialized cells take on individual characteristics and reach a specific form and function) into other types of cells, such as muscle cells. Thus, satellite cells act as a source of new nuclei for the muscle fibers, which helps the muscles meet the increased demands of larger muscle cells. 

Satellite cells are located between the basal lamina (basement membrane) and the plasma membrane (sarcolemma) of their associated muscle fiber. In adult muscle, these cells typically remain in an inactive, quiescent state (a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide). However, in response to injury or disease, the following immune and hormonal response activates these satellite cells. This causes them to proliferate (increase in number) in the injury location and/or differentiate. Myoblasts, the progeny cells (daughter cells), are able to:

  1. Fuse with each other to form new myofibers.
  2. Fuse to an existing muscle fiber.
  3. Return to the quiescent state and replenish the resident pool of satellite cells via self-renewal.

Once the satellite cells have fused to the muscle fiber, they donate their nuclei. These additional nuclei allow the muscle fiber to synthesize more proteins as well as create new actin and myosin filaments (active structures responsible for muscle contractions). As a result, the myofibrils (long filaments found in striated muscle cells) inside a muscle cell increase in both thickness and number, leading to increases in the muscle’s cross-sectional area (hypertrophy). Interestingly, more satellite cells are found associated with slow-twitch muscle fibers within the same muscle. This is because these fibers are activated more often during daily activities.

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Satellite Cells

Unspecialized stem cells with an ability to self-renew & develop into many different cell typesLocated in the periphery of muscle Activated by inflammation due to muscle damageFuses into muscle fibers and acts as a source of new nucleiPlays a crucial role in muscle regeneration and growth

Satellite cells and aging

Muscle strength has a strong connection to better quality of life and lower mortality. This is especially apparent among the older population suffering from sarcopenia (age-related loss of muscle function and mass). Sarcopenia is a progressive muscle disorder that is associated with higher likelihood of falls, fractures, physical disability, and mortality. These adverse putocmes are largely due to atrophy of stabilizing muscles and lowered grip strength. Together with osteoporosis (age-related loss of bone density), sarcopenia poses a genuine health risk for the elderly population.

Although the underlying mechanisms of sarcopenia are complex, one possible contributor to this is impaired satellite cell function. In fact, studies have proven that satellite content declines with age, which in turn contributes to muscle fiber atrophy. This decline in satellite cell number and function coincides with the gradual muscle loss that begins at around 30 years of age. Recent evidence suggests that a significant number of the aged satellite cells switch from the reversible quiescent state to a senescence state (the cell stops dividing and permanently withdraws from the cell cycle). Thus, preventing proliferation and renewal of the satellite cell pool. It is likely that this loss of satellite cell function reduces the ability to repair or replace muscle tissue that is lost in sarcopenia. 

On a positive note, the effects of sarcopenia can be significantly attenuated by exercise. Regular physical activity has been shown to increase muscle strength, enhance bone strength and density, improve flexibility, as well as maintain cognitive function. How much of this is attributed to satellite cell function in response to exercise is still relatively unknown and requires further research.

Final thoughts

Once a muscle experiences an injury, it undergoes a regeneration process that occurs in three sequential and overlapping stages: 1) the inflammatory and hormonal response; 2) the activation, differentiation, and fusion of satellite cells; and 3) the maturation and remodeling of newly formed myofibers (muscle fibers – rod-like organelles of a muscle cell). As we learned above, satellite cells are at the very heart of this important healing process.

Although our understanding of satellite cells has improved significantly over the last decades, many mechanisms behind their age-related decline remain to be discovered. 

Did you learn anything new about satellite cells? Let us know in the comments. 

Sources

  • Abreu P, Kowaltowski AJ. Satellite cell self‐renewal in endurance exercise is mediated by inhibition of mitochondrial oxygen consumption. Journal of cachexia, sarcopenia and muscle. 2020 Dec;11(6):1661-76.
  • Alway SE, Myers MJ, Mohamed JS. Regulation of satellite cell function in sarcopenia. Front Aging Neurosci. 2014 Sep 22;6:246. doi: 10.3389/fnagi.2014.00246. PMID: 25295003; PMCID: PMC4170136.
  • Chang NC, Rudnicki MA. Satellite cells: the architects of skeletal muscle. Current topics in developmental biology. 2014 Jan 1;107:161-81.
  • Chen W, Datzkiw D, Rudnicki MA. Satellite cells in ageing: Use it or lose it. Open biology. 2020 May 20;10(5):200048.
  • Charge, S. B. P., and Rudnicki, M.A. (2004). Cellular and molecular regulation of muscle regeneration. Physiological Reviews, Volume 84, 209-238.
  • Dumont NA, Bentzinger CF, Sincennes MC, Rudnicki MA. Satellite Cells and Skeletal Muscle Regeneration. Compr Physiol. 2015 Jul 1;5(3):1027-59. doi: 10.1002/cphy.c140068. PMID: 26140708.
  • Kadi F, Charifi N, Denis C, Lexell J, Andersen JL, Schjerling P, Olsen S, Kjaer M. The behaviour of satellite cells in response to exercise: what have we learned from human studies?. Pflügers Archiv. 2005 Nov;451(2):319-27.
  • Morgan JE, Partridge TA. Muscle satellite cells. Int J Biochem Cell Biol. 2003 Aug;35(8):1151-6. doi: 10.1016/s1357-2725(03)00042-6. PMID: 12757751.
  • Snijders T, Nederveen JP, McKay BR, Joanisse S, Verdijk LB, van Loon LJ, Parise G. Satellite cells in human skeletal muscle plasticity. Frontiers in physiology. 2015 Oct 21;6:283.
  • Sousa-Victor, P., Gutarra, S., Garcia-Prat, L., Rodriguez-Ubreva, J., Ortet, L., Ruiz-Bonilla, V., et al. (2014). Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 506, 316–321. doi:10.1038/nature13013
  • Yin H, Price F, Rudnicki MA. Satellite cells and the muscle stem cell niche. Physiol Rev. 2013 Jan;93(1):23-67. doi: 10.1152/physrev.00043.2011. PMID: 23303905; PMCID: PMC4073943.

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