This is part seven of a series of blogs from attendees at ACSM's Conference on Integrative Physiology of Exercise. The following blog is a reflection on the symposium titled "Molecular Transducers of Exercise-induced Muscle Hypertrophy" by Sarah Little. 

On the last day of the Integrative Physiology of Exercise conference in San Diego, Marcas Bamman, Ph.D., from the University of Alabama-Birmingham, chaired the symposium on Molecular Transducers of Exercise-induced Muscle Hypertrophy. Normally, I would be pretty intimated by a symposium on muscle biology and molecular pathways. However, this highly respected panel of scientists led talks that were complex yet easy to follow.

Overall, the main take away from the session was that exercise leads to the activation of multiple molecular pathways that are being unraveled by absolute geniuses in order to better understand how to grow and maintain muscle mass over the lifespan. 

Scott Trappe, Ph.D., FACSM, of Ball State University opened the symposium with a series of findings describing the transcriptome response to exercise in the aging athlete. Using a life-long exercise model, Dr. Trappe’s group looked at the differences between life-long exercisers, old healthy and young exercise subjects. As expected, the young athletes showed greater VO₂Max and muscle cross sectional area than life-long exercisers, but these life-long exercisers demonstrated exercise capacity and skeletal muscle health indices that were far superior to untrained old healthy subjects. Interestingly, this same hierarchical pattern was seen with fast fiber responsiveness to exercise, as well as transcriptome coordination and effectiveness, suggesting a preservation of a muscle metabolic phenotype with exercise through aging. Further, through analyzing the transcriptome signatures of each subject group, it was discovered that the function of the responding genes varies with age and exercise, with young exercisers primarily involving growth, life-long exercisers involving metabolism and the old healthy involving stress. Overall, Dr. Trappe’s group demonstrated, both at the molecular and functional levels, that exercise really is medicine.

Blake Rasmussen, Ph.D., of the University of Texas Medical Branch – Galveston discussed the role of protein turnover and anabolic signaling in exercise-induced muscle hypertrophy. Dr. Rasmussen did an excellent job of “unpacking” and simplifying some complicated intracellular signaling pathways to focus on a few key components: insulin, mTORC1 activation and translocation, and specific effects of exercise on the mTOR signaling pathway. Together, these led to three main points:

1. both inactivity and aging have been linked to reductions in mTORC1 signaling and anabolic resistance,
2. physical activity, capillary density and muscle perfusion may all be predictive of anabolic resistance, and
3. genetic manipulation of the nutrient sensing anabolic pathway can lead to muscle hypertrophy, but without concurrent exercise, it cannot improve muscle function.

John McCarthy, Ph.D., of the University of Kentucky focused on the role of ribosome biogenesis in skeletal muscle hypertrophy. For someone who has never heard of ribosome biogenesis, Dr. McCarthy provided a wonderfully clear explanation of the various methodologies to measure ribosomal RNA from in-vitro to in-vivo models, as well as the translational application of the resulting data. Linking back to muscle hypertrophy, several human and animal studies were described focusing on the effects of resistance exercise and rDNA transcription (to rRNA) and the translation of key ribosomal proteins. Interestingly, exercise-induced increases in ribosomal content (i.e. rRNA abundance) are highly correlated with the magnitude of muscle hypertrophy, and the inhibition of ribosome biogenesis prevents hypertrophy of myotubes in vitro.

Last but not least, Marni Boppart, Sc.D., FACSM, of the University of Illinois-Champaign-Urbana spoke on integrin regulation of muscle growth. Using knock out and transgenic mouse models, Dr. Boppart’s research has elucidated the mechanisms with which integrin, specifically the α7β1 complex, maintains cellular integrity and interacts with the mTOR signaling pathway to alter adaptation. While it does not facilitate load-induced growth via mTORC1, the α7β1 integrin complex may enhance growth via preservation of mTORC2 localization and signaling.

Though all four presentations had varying areas of emphasis among molecular transducers, the main take away was clear: Exercise regulates multiple molecular mechanisms in skeletal muscle, which may be protective or preventative with aging. Ultimately, this symposium fit wonderfully within ACSM’s emphasis of exercise as medicine, while summarizing groundbreaking new studies that will help to further understand the biology of muscle hypertrophy.

Read part 1 of this series: "Can Exercise Fill the Reductionist Gap? Reflections on Dr. Michael Joyner's Keynote."
Read part 2 of this series: "Are Exercise 'Mimetics' a Realistic Substitute for Exercise Training? Reflections on the Debate." 
Read part 3 of this series: "Exercise and Energy Restriction to Improve Health: Recent Research." 
Read part 4 of this series: "Molecular Transducers of Physical Activity (MoTrPac) Update." 
Read part 5 of this series: "Metabolic Flexibility in Health & Disease: A Symposium Summary." 
Read part 6 of this series: "How Exercise Promotes Brain Health in Aging." 


Sarah Little is a doctoral student at Texas A&M University. She earned her Bachelor of Science degree from Virginia Tech and her Master of Science in Kinesiology with an emphasis in Exercise Physiology from Texas A&M University.