While Myc concentrations in muscle are normally low, they rise with growth stimuli, such as exercise. Based on this observation and the fact that Myc stimulates many growth processes, researchers hypothesized that Myc was also crucial for skeletal muscle growth, called hypertrophy. To test this hypothesis, scientists of the Biozentrum, University of Basel, either depleted or elevated Myc levels in the muscle fibers of mice. The findings of the study have now been published in "Nature Communications".
Overproduction of Myc has consequences
The study shows that Myc in muscle fibers is not necessary for postnatal muscle growth or load-induced hypertrophy. Contrary to expectations, increasing Myc levels also did not cause muscle fibers to grow. Instead, high Myc levels strongly suppressed genes coding for the proteins that allow muscles to contract.
“To develop therapeutic approaches that improve muscle function, it is crucial to understand what makes muscles grow," explains Daniel Ham, first author of the study. "Rather than driving muscle fiber growth, our study shows that high Myc levels stop muscle fibers from expressing the genes that are important for muscle function.”
Myc is important for regeneration
However, Myc is still very important: In muscle stem cells, Myc expression was crucial for these cells to expand their number and fuse with muscle fibers to support muscle growth and regeneration. “Without Myc, muscle stem cells lost their ability to contribute to strong muscle growth or regenerate after an injury,” says Ham.
Implications for new therapies
“While our studies are important because they challenge the long-standing hypotheses about Myc’s role in skeletal muscle growth, they also highlight its important function within muscle stem cells for muscle growth and repair" says Prof. Markus Rüegg. "This study may also open new avenues for the development of therapies that balance Myc’s beneficial and harmful effects in muscle."
Original publication:
Daniel J. Ham, Michelangelo Semeraro, Bianca M. Berger, Timothy J. McGowan, Shuo Lin, Eleonora Maino, Filippo Oliveri, Markus A. Rüegg. Muscle fiber Myc is dispensable for muscle growth and its forced expression severely perturbs homeostasis. Nature Communications, published April 2025.
Contact: Communications, Heike Sacher