Hey Readers! Glad you are here! This is part III of my 5-part series on gluteal amnesia. If you have not read part 1 (click here) or part 2 (click here), I highly recommend that you go back and read those parts before delving deeper into the information presented here. In this series, I am taking a deep dive into the phenomenon of gluteal amnesia. If you recall from parts I and II, gluteal amnesia is a condition where the gluteal muscles become weakened and/or underactivated due to injury/pain, poor posture, and/or lack of use. The implications of gluteal amnesia are far-reaching, affecting nearly all other functional movements in your body. In this part, I will go over the cellular changes that can occur in the gluteal muscles as a result of gluteal amnesia. I will discuss the difference between muscle atrophy and hypertrophy and the cellular mechanisms therein. I’ll be honest, this part consists primarily of cellular biology information, but I have tried to simplify this information as best I can so you can get the most important points as it pertains to gluteal amnesia.
Muscle tissue, like most tissues in your body, is constantly changing to adapt to the demands, or lack thereof, placed upon it. Muscles can grow larger in size (known as hypertrophy) when stimulated with an adequate load, and muscles can shrink in size (known as atrophy) as a result of many factors. The image below illustrates the basic concept of atrophy and hypertrophy. Please keep in mind, skeletal muscle cells are actually cylindrical in shape and not spherical, as depicted in the image.
The cellular pathways that control and regulate muscle atrophy and hypertrophy are quite complex, so I am going to be simplifying it quite a bit to explain the most crucial parts. Let’s first start with a general overview of atrophy and hypertrophy before diving deeper into the cellular biology of muscle change.
Relationship Between Muscle Size and Lifestyle
Skeletal muscle undergoes continuous turnover to adapt to changes from its mechanical environment. In general, mechanical overload increases muscle mass and mechanical underload decreases muscle mass.
Skeletal muscle hypertrophy is well documented in individuals who train with the appropriate load (i.e. resistance), intensity, and frequency. Skeletal muscle hypertrophy occurs when the load placed upon a muscle is so much that it actually forces the muscle tissue to adapt by getting bigger.
Skeletal muscle atrophy as a result of disuse or injury is well documented. For example, studies have shown that prolonged muscle disuse (such as what the diaphragm experiences with patients on mechanical ventilation or what patients experience when a body part is immobilized after injury) leads to the activation of muscle atrophy pathways. Atrophy in the gluteal muscles has also been documented in people with gluteal amnesia. For example, one study found that the cross sectional area (CSA) of the gluteus maximus was significantly less in women with gluteal amnesia compared to healthy controls, as measured using pelvic CT scans. Other studies have shown that a loss neural input to the gluteal muscles leads to muscle atrophy. Thus, it is well established that if you do not use a muscle, for whatever reason (e.g. injury, immobilization, chronic disuse, etc.), it is likely to atrophy, get weaker, and not produce force efficiently for movement.
What Actually Happens in Muscle Atrophy?
Muscle atrophy is characterized by a decrease in the cross sectional area (CSA) of a muscle due to excessive protein degradation without a corresponding increase in protein synthesis. The muscle cell actually shrinks in size because cytoplasm (i.e. the fluid found within a cell), proteins, and various organelles (i.e. structures within the cell that perform a specific job) are broken down in a process known generally as catabolism. Catabolism is a process whereby complex molecules get brown down into simpler ones with a concomitant release of energy.
There are certain proteins within the muscle cell, organized into repeating structures known as sarcomeres, that are responsible for creating muscle contraction and generating force (e.g. click here to read more about sarcomeres and muscle contraction).
During muscle atrophy, these proteins are typically catabolized, or broken down, first. When these sarcomeric proteins are catabolized, the muscle will not be able to generate sufficient force for functional movements. For example, if your gluteal muscles atrophy, they will not be able to generate enough force to help you stand up from a seated position, causing your low back and hamstring muscles to pick up the slack (see part II of this series for more information on this). Skeletal muscle atrophy is often seen in disease, aging, injury, nutritional decrements, and disuse (e.g. bed rest, cast immobilization due to injury, spinal cord injury, weightlessness environments, sedentary lifestyle, etc.).
At the cellular level, muscle atrophy is controlled by two different pathways – the ubiquitin-proteasome pathway (UPP) and the autophagy-lysosome pathway (ALP). These two pathways are the most important operations that control protein and organelle turnover in a muscle cell. Both of these pathways involve the attachment of multiple copies of a protein called ubiquitin to a protein or organelle (aka “polyubiquination”), labeling it for destruction inside the cell. Depending on the specific configuration of the ubiquitin (Ub) molecules (known as the “ubiquitin code”), the protein/organelle will either be catabolized by the UPP or the ALP. In general, the UPP is mostly responsible for breaking down various proteins within the cell, while the ALP is primarily responsible for catabolizing damaged/unused organelles (e.g. mitochondria).
In the Ubiquitin-proteasome pathway (UPP), proteins that are marked for destruction are sent to a large, catalytic protein, known as a proteasome (specifically “26S proteasome”), where they are broken down into their constituent parts (i.e. amino acids). The 26S proteasome does not just degrade any protein; it specifically recognizes proteins that have been polyubiquinated (i.e. marked for destruction) with the specific ubiquitin code for the UPP. When your gluteal muscles are not used or stimulated adequately, the UPP will catabolize sarcomeric proteins (e.g. actin, myosin, titin, etc. - click here to read more about these proteins) and other proteins in those muscle cells.
In the Autophagy-lysosome pathway (ALP), the polyubiquinated cargo is delivered to a cellular structure known as a lysosome, which is an organelle responsible for digestion within the cell. Lysosomes are sort of like the “stomach of the cell.” Autophagy, defined as “self-digestion,” is used to describe this process since one cell organelle digests another organelle from the same cell. Typically the ALP breaks down cellular organelles, such as mitochondria (singular - mitochondrion), using various acid hydrolases (similar to what happens in the stomach).
The breakdown of mitochondria is of particular importance in the gluteal muscle cells because mitochondria are considered the “powerhouse of the cell.” This nickname is given because mitochondria generate most of the energy needed to power all the operations occurring in the cell. Mitochondria are known for creating ATP molecules (i.e. adenosine triphosphate) which store chemical energy for future use by the cell.
There are typically many copies of mitochondria inside a single muscle cell, and disruption of this mitochondrial network is a crucial part of muscle atrophy in the glutes. When the number of mitochondria decrease in an atrophying gluteal muscle, that muscle tissue fatigues much faster since there is less capability to produce ATP to sustain longer bouts of physical activity. For example, if the mitochondria in your glutes breakdown, the gluteal muscles will not be able to sustain contraction during everyday activities (such as walking or standing). This will cause the synergist muscles to pick up the slack, potentially leading to pain or injury in those muscles. Remember, synergist muscles have their own jobs to do, and they are not designed to carry out the function of other muscles.
While protein and organelle breakdown is a negative thing during muscle atrophy, some protein and organelle turnover is crucial for homeostasis in the cell. Impairment of protein/organelle turnover can actually be quite harmful to the cell because damaged and dysfunctional organelles and proteins accumulate within the cell, interfering with the normal structure and function of the cell. In a muscle cell, this can cause weakness and reduced force output. Thus, some turnover is not only normal, it’s downright essential for the health of a muscle cell. Recent evidence has demonstrated a link between physical exercise and autophagy in muscle, where physical exercise is very effective in stimulating autophagy in skeletal muscles (i.e. breakdown of damaged organelles in the lysosome), removing old, nonfunctional, and damaged organelles.
What Actually Happens in Muscle Hypertrophy?
In contrast to muscle atrophy, hypertrophy occurs when there is an increase in the CSA of a skeletal muscle due to higher rates of protein synthesis compared to protein breakdown. In muscle hypertrophy, various proteins and organelles are synthesized from smaller molecules in a process known as anabolism. Muscle hypertrophy typically occurs as a result of exercise or physical activity and usually only occurs if the exercise provides the appropriate intensity, duration, and frequency. If a physical activity provides the skeletal muscle with the appropriate stimulation, the muscle will quite literally be forced to adapt (by getting bigger) to meet the demand of the exercise or activity. In addition to the CSA of muscle increasing as a result of exercise, exercise also increases the capillary density of muscles (so muscles get better blood flow) and the mitochondrial density within the cell (increasing the muscle cell’s ability to produce energy).
Signals for protein synthesis and muscle growth include stimulatory factors such as mechanical loading of the muscle (e.g. exercise), hormone circulation, and nutrition. Skeletal muscle growth, or hypertrophy, is primarily mediated by growth hormone (GH) and insulin-like growth factor 1 (IGF-1). GH, secreted by the pituitary gland in the brain, is a hormone responsible for growth in animals, and it is typically released in response to exercise, sleep, and nutritious food intake. When GH is secreted by the pituitary gland, it stimulates the production of IGF-1. The liver is the primary organ responsible for producing IGF-1, producing nearly 75% of the total IGF-1 in the body. Once synthesized, IGF-1 circulates in the bloodstream, where it can act on various tissues, such as the gluteal muscles, bone, and adipose (i.e. fat) tissue.
IGF-1 essentially has three effects that result in muscle growth, or hypertrophy. One, when IGF-1 binds to receptors on a skeletal muscle cell, it activates a special enzyme known as Mammalian Target of Rapamycin, or mTOR. Within the muscle cell, mTOR stimulates the building of proteins from amino acids, elongates proteins already built, and helps to build ribosomes (i.e. organelles involved in protein production inside the cell). Two, IGF-1 inhibits, or blocks, catabolic pathways inside the cell, such as UPP and ALP described above. Third, IGF-1 activates specialized muscle cells known as satellite cells. The activated satellite cells can fuse with muscle cells to help synthesize new myofibrils, which are the long, thread-like parts of muscle cells responsible for contraction. Myofibrils contain sarcomeres, which are the contractile unit a muscle cell (click here to read more about this). When you provide appropriate mechanical stimulation to your gluteal muscles (via movement and physical activity - part V of this series will cover this in more detail), it can lead to muscle growth via the production and enhancement of proteins within the gluteal muscle cells.
In addition to muscle hypertrophy, exercise also stimulates the production of more mitochondria inside the muscle cell. Recall, mitochondria are the place where most of the cell’s energy is generated, so more mitochondria means more available energy inside the cell. Exercise is correlated with increased levels of a protein known as mitochondrial transcription factor A, or TFAM, in skeletal muscle. In fact, TFAM levels increase after a single, 15-minute bout of endurance exercise. TFAM plays a role in mitochondrial biogenesis, or creating new copies of mitochondria, and exercise has been suggested to increase mitochrondrial volume by up to 40% inside the muscle cell. Thus, exercising your gluteal muscles can stimulate production of more mitochondria inside the gluteal muscle cells, giving those muscles more energy to use as fuel in functional movements.
Summary
Muscle is a very plastic tissue, constantly undergoing remodeling in order to meet the demands placed on it. Muscle atrophy is characterized by a decrease in the CSA of the muscle, and is typically brought about by injury, disuse, aging, disease, and nutritional decrements. Several studies have documented muscle atrophy in gluteal amnesia. The decrease in muscle size is due to excessive breakdown of intracellular proteins, fluids, and organelles. There are two pathways that are primarily responsible for muscle atrophy – the ubiquitin-proteasome pathway (UPP) and the autophagy-lysosome pathway (ALP). In each pathway, the structure to be broken down gets labeled with several copies of ubiquitin and either gets broken apart by the 26S proteasome or digested within the lysosome of the cell. Typically, sarcomeric proteins (i.e. proteins involved in muscle contraction) and mitochondria are broken down or digested in muscle atrophy, reducing the ability of the gluteal muscles to produce, and maintain, force in everyday movements. Muscle hypertrophy, in contrast, is characterized by an increase in the CSA of the muscle, and is typically brought on by exercise, nutrition intake, and hormones. The GH/IGF-1 pathway is the main system responsible for triggering the production of proteins, leading to muscle hypertrophy. TFAM, a protein that regulates mitochondria biogenesis, is produced in response to exercise, leading to increased numbers of mitochondria, and subsequently energy, inside the gluteal muscle cells. You must provide adequate stimulation to your gluteal muscles, or they are likely to atrophy. Part IV of this series will dive deeper into the neurobiology of gluteal amnesia, and part V of this series will discuss various exercises and lifestyle practices that can help ward off gluteal amnesia and the effects therein.
Please note, the information presented in this blog series is not meant to diagnose gluteal amnesia or treat active cases of gluteal amnesia. After reading this series, if you have concerns about your gluteal muscles, please follow up with your physician, physical therapist, or sports medicine doctor. If you have been diagnosed with gluteal amnesia, please continue to heed the advice of the medical professional that evaluated you. Also, please keep in mind that I have simplified some anatomical and biological information, so I can keep the focus on gluteal amnesia as best I can. If you feel like you need more thorough descriptions and explanations, please refer to my reference list at the end of each installment in this series. Also, a special thanks to my amazing husband for doing all of the artwork for this post. Matt - you truly are a very talented artist.
As always, the information presented in this blog post is derived from my own study of neuroscience, human movement, anatomy, and yoga. If you have specific questions about your gluteal muscles, please consult with your physician, physical therapist, or private yoga teacher. If you are interested in private yoga sessions with me, Jackie, you can book services on my website ("Book Online" from the menu at the top of the page), or you can email me at info@lotusyogisbyjackie.com for more information about my services. Also, please subscribe to my website so you can receive my weekly newsletters (scroll to the bottom of the page where you can submit your email address). This will help keep you "in-the-know" about my latest blog releases and other helpful yoga and wellness information. Thanks for reading!
~Namaste, Jackie Allen, M.S., M.Ed., CCC-SLP, RYT-200, RCYT, NASM-CPT
References:
Amabile, A.H., Bolte, J.H., & Richter, S.D. (2017). Atrophy of gluteus maximus among women with a history of chronic low back pain. PLOS One. p. 1 – 12.
Banaldo, P. & Sandri, M. (2013). Cellular and molecular mechanisms of muscle atrophy. Disease Models & Mechanisms. 6: 25 – 39.
Bento, J. (n.d.). Glute Training for Real-Life Strength. Breaking Muscle. Available here.
Biel, A. (2014). Trail Guide to the Body: A hands-on guide to locating muscles, bones, and more – 5th Edition. Books of Discovery. Boulder, CO.
Buckthorpe, M., Stride, M., & Della Villa, F. (2019). Assessing and treating gluteus maximus weakness – a clinical commentary. The International Journal of Sports Physical Therapy. 14(4): 655 – 669.
Clark, M.A. et al. (2018). NASM Essentials of Personal Fitness Training. 6th Edition. Jones & Bartlett Learning. Burlington, MA.
Freeman, S., Mascia, A., & McGill, S. (2013). Arthrogenic neuromusculature inhibition: A foundational investigation of existence in the hip joint. Clinical Biomechanics. 28: 171 – 177.
Gabriel, C. (2019). If You Sit at a Desk all Day, This Muscle Might be in Danger. Ortho Carolina. Available here.
Gordon, T., & English, A.W. (2016). Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise. European Journal of Neuroscience. 43(3): 336 – 350.
James, J. (2017). Gluteal Amnesia. Back Forever. Available here.
Marieb, E.N. (2004). Human Anatomy & Physiology – 6th Edition. Pearson Education, Inc. San Francisco, CA.
Messi, M.L., et al. (2016). Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults. Journals of Gerontology: Biological Sciences. 71(10): 1273 – 1280.
Muller, P., et al. (2020). Lactate and BDNF: Key Mediators of Exercise Induced Neuroplasticity? Journal of Clinical Medicine. 9(1136): 1 – 15.
Natarajan, A., Sethumadhavan, A., & Krishnan, U.M. (2019). Toward Building the Neuromuscular Junction: In Vitro Models to Study Synaptogenesis and Neurodegeneration. ACS Omega. 4: 12969 – 12977.
Neto, W.K., et al. (2020). Gluteus Maximus Activation during Common Strength and Hypertrophy Exercises: A Systematic Review. Journal of Sports Science and Medicine. 19: 195 – 203.
Roland, J. (2019). All About Gluteal Amnesia (‘Dead Butt Syndrome’). Healthline. Available here.
Schiaffino, S., et al. (2013). Mechanisms regulating skeletal muscle growth and atrophy. FEBS Journal. 280: 4294 – 4314.
Shors, T.J., et al. (2012). Use it or lose it: How neurogenesis keeps the brain fit for learning. Behavioral Brain Research. 227(2): 450 – 458.
Sonenblum, S.E., et al. (2020). Seated buttocks anatomy and its impact on biomechanical risk. Journal of Tissue Viability. 29: 69 – 75.
Stastny, P. et al. (2016). Strengthening the Gluteus Medius Using Various Bodyweight and Resistance Exercises. Strength and Conditioning Journal. 38(3): 91 – 101.
Theilen, N.T., Kunkel, G.H., & Tyagi, S.C. (2017). The Role of Exercise and TFAM in Preventing Skeletal Muscle Atrophy. Journal of Cell Physiology. 232(9): 2348 – 2358.
Wisdom, K.M., Delp, S.L., & Kuhl, E. (2015). Use it or lose it: Multiscale skeletal muscle adaptation to mechanical stimuli. Biomechanics and Modeling in Mechanobiology. 14(2): 195 – 215.
Yoo, W. (2016). Effects of bridging plus exercises with heel lift on lower extremity muscles. The Journal of Physical Therapy Science. 28: 1582 – 1583.
Comments