Some people are born with a large muscle mass whereas others are born with little muscle. Today we know that the variation in muscle mass depends a lot on what you inherit from your mum and dad. But, what are the genes that determine muscle mass? To address this question, Sander Verbrugge together with a host of co-authors systematically screened the literature for studies where the experimental loss or gain-of-function resulted in significant skeletal muscle hypertrophy in mice. We found 47 genes that meet our search criteria and cause muscle hypertrophy after gene manipulation. We then also analysed these genes further to see whether these are muscle genes, whether they are activated by exercise and whether they have all similar functions.
To get more information on his work we interviewed Sander Verbrugge after publishing his first paper.
Sander, congratulations that your systematic review is accepted now. How much work was it?
Since the start of my PhD, a year and a half ago, I’ve been working on this review. I wanted to create a reference for the muscle field that contains a comprehensive overview of genes that regulate muscle mass. Most of the time I spent on reading the papers, and extracting relevant information in an Excel file that became supplementary table S2 for the review. I wanted to make the table as complete as possible including any other measurements performed in the studies. This I did to make it possible for others to discover patterns between ‘hypertrophy-genes’ that we perhaps did not find. I hope the review is useful for many, and that it saves others in the field the effort of reading all the individual ‘hypertrophy papers’. I identified 47 genes whose gain or loss-of-function increases skeletal muscle in mice.
What is the main take home message? Is there anything that has surprised you?
Skeletal muscle mass can be regulated on different levels. The manipulation of genes encoding for kinases, cytoskeleton proteins, transcription factors, ligases, mitochondrial proteins, membrane receptors, nuclear receptors can all potentially increase muscle mass. Still, we found that mainly three signalling pathways can induce hypertrophy. These are 1) Igf1-Akt-mTOR, 2) myostatin-Smad, and 3) angiotensin-bradykinin signalling. In addition, we found that several ‘hypertrophy genes’ change their expression after resistance exercise, maximal muscle contraction or in overloaded mouse muscle. One thing that surprised me is that many of the hypertrophy genes are low expressed in skeletal muscle compared to other tissues. Still, manipulation of these low expressed genes can induce muscle growth.
What is the practical use of this work?
The muscle hypertrophy genes we identified are candidate genes that can potentially be targeted for drug discovery in the treatment of several muscle diseases and sarcopenia.
Sander Verbrugge started in the autumn of 2016 as a PhD student in the Exercise Biology team. We are glad that his first publication is accepted at the half way mark of his PhD. And last but least, we would also like to thank the other authors and especially Dr. Lore Becker and Prof. Dr. Martin Hrabě de Angelis for a great collaboration between the TUM Exercise Biology team and the German Mouse Clinic. If you are interested, here is the link to Frontiers in Physiology where the paper is published.