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Knowing how MYC promotes muscle growth can be crucial for developing treatments that mitigate age-related muscle loss, thereby enhancing independence, mobility, and overall health.
For some time, it has been recognized that there is a connection between the MYC gene, which is linked to cancer, and how muscles adapt to exercise. After physical activity, MYC levels in human muscles temporarily increase over a span of 24 hours. However, this response diminishes as we age, which may contribute to the challenges of muscle recovery and maintenance.
Understanding the intricate workings of MYC in muscle growth could be vital for developing therapies aimed at counteracting muscle loss associated with aging, potentially resulting in better independence, mobility, and health.
A recent study published in EMBO Reports has shed new light on MYC’s function within skeletal muscle. This research involved 20 authors from five different institutions: the U of A, Karolinska Institute in Sweden, Linköping University in Sweden, Oakland University, and the University of Kentucky.
With a diverse group of contributors, the paper is filled with insightful data that can be summarized in two main sections. The first part presents a 24-hour examination of the molecular changes in human muscles after resistance exercise. The second part investigates whether specific levels or “pulses” of MYC in skeletal muscles can encourage muscle growth without the need for exercise. The answer to that is a resounding yes.
The Molecular Landscape of MYC
Ronald Jones, a co-first author and Ph.D. candidate at the U of A’s Department of Health, Human Performance and Recreation, pointed out that most studies typically take muscle samples before exercise and only a few hours later. By performing multiple biopsies over 24 hours, overseen by their Swedish colleagues, the researchers were able to gain a comprehensive view of how the body adjusts to exercise over time and identify which genes play crucial roles in this adaptation.
“Our data shows that the peak responsiveness actually occurs eight hours post-exercise,” Jones stated. “We found that MYC was the third most significant molecule three hours after working out, and it became the most crucial at the eight and twenty-four hour marks. This highlights the importance of timing in mapping the body’s acute exercise responses.”
Once the researchers comprehended the molecular processes occurring in human muscles, they focused on isolating MYC to thoroughly investigate its role in promoting muscle growth. This was achieved by genetically regulating MYC levels in specialized mouse models. These mice were not given access to an exercise wheel, which typically enhances muscle growth, but were free to move around normally otherwise.
Samples taken from the mice’s soleus muscles, which are essential for basic activities like standing or walking, revealed that MYC alone boosted muscle mass and fiber size in these muscles compared to genetically identical mice that did not receive MYC treatments but lived under the same conditions. Consequently, the researchers effectively replicated the exercise response without requiring actual exercise.
The Implications of MYC
These findings strengthen the argument that MYC plays a vital role in muscle growth resulting from resistance training. However, MYC is unlikely to serve as a basis for new therapies for sarcopenia or to become a performance-enhancing substance. It regulates about 15 percent of an estimated 20,000 human genes, potentially leading to unpredictable effects on many other genes. Being a potent oncogene, MYC’s ability to promote muscle growth could also trigger unwanted cellular proliferation in organs like the liver, leading to tumor development. Using MYC alone could result in serious and fatal side effects.
Kevin Murach, an assistant professor at the U of A and Jones’ advisor, who is a senior and corresponding author of the study, remarked that “it’s fascinating that a factor associated with cancer also modulates the muscle growth response to exercise. This suggests a common regulatory mechanism, indicating that ‘growth is growth.’
Murach further explained, “The key takeaway isn’t necessarily that we should increase MYC in muscles to mimic exercise. Instead, we can leverage our understanding of how this oncogene influences muscle tissue and work toward designing treatments for muscle atrophy and improving muscle adaptability that activate the beneficial effects of MYC without triggering oncogenesis.”
In addition to being an oncogene, MYC is one of four Yamanaka factors, which are protein transcription factors that can revert specialized cells (like skin cells) back to a more youthful, adaptable stem cell state. When applied in appropriate doses, these factors can counteract the effects of aging in rodents by mimicking the flexibility seen in younger cells.
Among these four factors, only MYC is activated by exercising skeletal muscle. This discovery provides further incentive for researchers to explore MYC’s role in muscle as it relates to aging and exercise.
Looking ahead, Jones plans to continue investigating the complexities of MYC as the main focus of his dissertation. “I’m incredibly passionate about it,” he shared. “I wake up every day thinking about this project. I truly enjoy it, and I believe MYC is one of the most influential molecules in muscle tissue… yet there is still so much left to uncover.”
Joining Jones and Murach as co-authors from the U of A are Sabin Khadgi, a muscle physiology research technician; PJ Koopmans, a Ph.D. candidate; Toby Chambers, a post-doctoral fellow; Francielly Morena, a recent U of A Ph.D. graduate; and Nicholas Greene, a professor and director of the Exercise Science Research Center.
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