Megan Chu, Class of 2021
Muscle atrophy is a condition where muscle is broken down to conserve energy. It is the result of lack of mobility, which can be due to a variety of factors such as aging, genetics, bedrest due to illness, poor nutrition, neuronal injury or disease, or from experiencing microgravity in space (1). Although recovery is possible, sometimes minor cases of muscle atrophy can result in some permanent loss of muscle movement and strength. Furthermore, there aren’t many options for treatment; available treatments usually depend on the severity of the atrophy and include physical therapy, surgery, or dietary changes (1).
Unlike humans, animals that hibernate throughout the year do not display the same level of muscle deterioration after months of inactivity. Hibernation is not simply a “deep sleep,” rather it is an adaptive technique evolved to conserve energy during periods of extreme conditions. Though the common example is bears and other animals that hibernate through the winter, some animals also hibernate during long droughts or extended periods of extreme temperatures. (3) During hibernation, the animal’s heartbeat can slow down to a mere few beats per minute while their metabolic processes also slow down by up to 75%. Blood glucose levels are maintained despite the complete lack of caloric intake (1). Urination and defecation also stop because these animals can reabsorb various nutrients from their waste products (3).
Grizzly bears, for example, hibernate for five to seven months out of the year. During this time, the bears do lose some muscle mass, but if a human were to remain inactive for the same amount of time, they’d lose twice as much muscle mass as the grizzly bear does (1). One possible explanation for this difference is the observed shivers, where the muscles are neutrally stimulated to contract periodically during hibernation.
Nevertheless, studying how metabolic pathways and gene expression are regulated in hibernating animals can help scientists develop more effective therapies to treat muscle atrophy and regain muscle mass after inactivity. Researchers at the Max Delbrueck Center for Molecular Medicine in Germany took muscle biopsy samples from grizzly bears before and after hibernation (1). They conducted proteomic and transcriptome analyses of the samples and compared the results to muscle tissues from worms, mice, and aging humans.
One difference they found was that the level of non-essential amino acids between bears during hibernation and aging humans. Eleven non-essential amino acids are not essential to the human diet because humans are capable of synthesizing them. Not only did aging humans display lower levels of six of these amino acids compared to the hibernating bears, but hibernating bears also displayed very high levels of the same non-essential amino acids (1). Grizzly bears, like other animals that hibernate, have evolved processes that allow them to reabsorb nutrients from their waste products (1). In this case, grizzly bears can reabsorb urea from urine, thus, they do not have to break down muscle to replenish their supply of amino acids. However, the proteins isolated from the muscle biopsies were not rich in non-amino acids. This suggests that these amino acids are not used to build important proteins, but act as substrates for important regulatory pathways (1). The scientists found that these non-essential amino acids increased the activity of a specific protein kinase called phospho-S6K during hibernation (1). Phospho-S6K is a protein that increases protein synthesis and cell proliferation. It is required to build muscle and is typically activated by physical activity (1). Furthermore, they treated mouse myoblasts—muscle embryonic progenitor cells—with non-essential amino acids and found that levels of phospho-S6K were higher and levels of proteins that are associated with atrophy were lower. Muscle fibers in these cells were thicker (1).
Their results point to an obvious treatment for muscle atrophy: if higher levels of non-essential amino acids can preserve muscle mass, all scientists have to do is devise supplements of these amino acids for humans to ingest. However, exogenously treating nematode C. elegans—which has often been used as a model to study neuromuscular disease—has shown no significant effect in preventing muscle atrophy (1). It seems as though there is something about the origin of these amino acids that affect its ability to upregulate pathways that are important for muscle growth. Externally supplementing non-essential amino acids does not result in the same degree of muscle retention. Therefore, attempting to create an endogenous supplement of these amino acids might be a more effective treatment for muscle atrophy because it better mimics the pathways the grizzly bear has evolved.
References
Unlike humans, animals that hibernate throughout the year do not display the same level of muscle deterioration after months of inactivity. Hibernation is not simply a “deep sleep,” rather it is an adaptive technique evolved to conserve energy during periods of extreme conditions. Though the common example is bears and other animals that hibernate through the winter, some animals also hibernate during long droughts or extended periods of extreme temperatures. (3) During hibernation, the animal’s heartbeat can slow down to a mere few beats per minute while their metabolic processes also slow down by up to 75%. Blood glucose levels are maintained despite the complete lack of caloric intake (1). Urination and defecation also stop because these animals can reabsorb various nutrients from their waste products (3).
Grizzly bears, for example, hibernate for five to seven months out of the year. During this time, the bears do lose some muscle mass, but if a human were to remain inactive for the same amount of time, they’d lose twice as much muscle mass as the grizzly bear does (1). One possible explanation for this difference is the observed shivers, where the muscles are neutrally stimulated to contract periodically during hibernation.
Nevertheless, studying how metabolic pathways and gene expression are regulated in hibernating animals can help scientists develop more effective therapies to treat muscle atrophy and regain muscle mass after inactivity. Researchers at the Max Delbrueck Center for Molecular Medicine in Germany took muscle biopsy samples from grizzly bears before and after hibernation (1). They conducted proteomic and transcriptome analyses of the samples and compared the results to muscle tissues from worms, mice, and aging humans.
One difference they found was that the level of non-essential amino acids between bears during hibernation and aging humans. Eleven non-essential amino acids are not essential to the human diet because humans are capable of synthesizing them. Not only did aging humans display lower levels of six of these amino acids compared to the hibernating bears, but hibernating bears also displayed very high levels of the same non-essential amino acids (1). Grizzly bears, like other animals that hibernate, have evolved processes that allow them to reabsorb nutrients from their waste products (1). In this case, grizzly bears can reabsorb urea from urine, thus, they do not have to break down muscle to replenish their supply of amino acids. However, the proteins isolated from the muscle biopsies were not rich in non-amino acids. This suggests that these amino acids are not used to build important proteins, but act as substrates for important regulatory pathways (1). The scientists found that these non-essential amino acids increased the activity of a specific protein kinase called phospho-S6K during hibernation (1). Phospho-S6K is a protein that increases protein synthesis and cell proliferation. It is required to build muscle and is typically activated by physical activity (1). Furthermore, they treated mouse myoblasts—muscle embryonic progenitor cells—with non-essential amino acids and found that levels of phospho-S6K were higher and levels of proteins that are associated with atrophy were lower. Muscle fibers in these cells were thicker (1).
Their results point to an obvious treatment for muscle atrophy: if higher levels of non-essential amino acids can preserve muscle mass, all scientists have to do is devise supplements of these amino acids for humans to ingest. However, exogenously treating nematode C. elegans—which has often been used as a model to study neuromuscular disease—has shown no significant effect in preventing muscle atrophy (1). It seems as though there is something about the origin of these amino acids that affect its ability to upregulate pathways that are important for muscle growth. Externally supplementing non-essential amino acids does not result in the same degree of muscle retention. Therefore, attempting to create an endogenous supplement of these amino acids might be a more effective treatment for muscle atrophy because it better mimics the pathways the grizzly bear has evolved.
References
- Eske J. 2019 May 30. Muscle atrophy: Causes, symptoms, and treatments. Medical News Today. [accessed 2020 Feb 22]. https://www.medicalnewstoday.com/articles/325316.php#causes
- Mugahid DA, Sengul TG, You X, Wang Y, Steil L, Bergmann N, Radke MH, Ofenbauer A, Gesell-Salazar M, Balogh A, et al. 2019 Dec 27. Proteomic and Transcriptomic Changes in Hibernating Grizzly Bears Reveal Metabolic and Signaling Pathways that Protect against Muscle Atrophy. Nature News. [accessed 2020 Feb 22]. https://www.nature.com/articles/s41598-019-56007-8
- Panko B. 2017 Jan 18. Can Humans Ever Harness the Power of Hibernation? Smithsonian.com. [accessed 2020 Feb 22]. https://www.smithsonianmag.com/science-nature/can-humans-ever-harness-power-hibernation-180961835/
Image Source: https://commons.wikimedia.org/wiki/File:Bear_Sleeping_(11842384304).jpg#filehistory
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