Dr. Blake Rasmussen currently holds the Lloyd and Sue Ann Hill Endowed Professorship in Healthy Aging at The University of Texas Medical Branch (UTMB), in Galveston. He also serves as Director of the Department’s Muscle Biology & Metabolism Laboratory and is the Leader of the NIH funded Claude D. Pepper Older Americans Independence Center Biology & Metabolism Core at UTMB. Dr. Rasmussen did his doctoral research in Zoology/Cell Biology at Brigham Young University. Before arriving at UTMB he was an assistant professor at the University of Southern California. His lab at UTMB focuses on muscle loss during aging and potential preventive measures.
Dr. Rasmussen’s talk focused on loss of skeletal muscle mass and function in normal aging, often referred to as sarcopenia. This loss in muscle mass contributes to frailty syndrome, which is an increase in the chance of a dramatic decline in health of older adults. Sarcopenia relates to low physical performance and can predict mortality in older adults (the stronger your muscles, the longer you should live). This loss of skeletal muscle size and function may be associated with an age-related muscle protein synthesis impairment. In human skeletal muscle, one of the pathways that is required for protein synthesis is mechanistic target of rapamycin complex 1 (mTORC1). When the mTORC1 pathway is induced, there is an increase in protein synthesis, which helps build stronger muscles. For more information on mTOR, visit our previous blogs, here and here. In his presentation, Dr. Rasmussen showed how nutrition and exercise could be strategically used to effect mTORC1 signaling and skeletal muscle protein synthesis to slow the progression of sarcopenia. One of the more unique aspects of Dr. Rasmussen’s research is that it focuses on actual human patients rather than just cell culture or model organisms. Although Dr. Rasmussen’s lab does make use of mice and rat models, their ability to monitor effects in actual human patients makes their research very translational to human application.
Q: We often hear all the conventional advice about diet and exercise to help with slowing the aging process, but what would be some unconventional advice you would give to people who wanted to slow the aging process and increase health span?
BR: I think the way we eat should be addressed. For instance, most individuals consume all of their daily protein at one, maybe two meals during the day. The problem is that only so much of that protein gets used, the rest then gets oxidized or potentially stored as fat. Usually the high protein meals are lunch and dinner, and dinner is often the meal with the least physical activity following it. This lack of physical activity following the meal results in even more of the protein being stored as fat instead of being immediately metabolized or used to maintain muscle mass. It would be better, I believe, if the protein intake was spread throughout the entire day, so each meal contained about 20-25g of protein. This isn’t very much protein, a 4oz chicken breast contains about 20g of protein. So perhaps a 30-30-30 plan, 30g of protein at each meal, breakfast, lunch, and dinner. It is possible that vegetarians might have to intake more protein, and certainly they will need to find a good source of protein.
Q: Of the canonical model organisms, you work with mouse and rat, but you also work with humans. Could you compare and contrast the major advantages of working in humans compared to working in mouse or rat models?
BR: I think what most people would consider the major limitation when working with humans is identifying specific mechanisms. Oftentimes the data you collect from human experiments can be descriptive or correlative, but harder to pinpoint the exact mechanism. In model organisms, however, you can directly manipulate a pathway by modifying a gene in the pathway. We can’t do this in humans. Alternatively, in animals it can be very hard to measure function, for example in sarcopenia the question arises how does one measure muscle health and strength, and how well does that correlate to a human.
Q: When you are not writing grants, papers or IRBS (Institutional Review Board, which examines ethics for human subjects), what do you do for fun?
BR: I like baseball and race cars. I used to play baseball as a kid, but now I watch more than play. I am a big LA Dodgers fan since I grew up listening to them on the radio, Fernando Valenzuela was the big star then. Now living in the Houston area, I have become an Astros fan as well, it is great having two different teams to cheer for on weekends. I actually do drive a race car in my spare time, a Boss 302 mustang, which I drive at the track with several friends of mine who also own race cars.
Q: What piqued your interest in muscle metabolism?
BR: As an undergraduate I took a course in exercise physiology and it was one of the few courses in which you could actually link what you are doing to what you are studying. I took a graduate course in endocrinology which furthered my interest in metabolism, and as a graduate student I did my dissertation on AMPK, exercise and muscle metabolism in a rodent model. As a postdoc I did my work in a large lab (about 20-30 postdocs/students/research scientists) with a focus on human metabolism. It was very competitive but also inspiring, interacting with so many scientists from around the world.
Q: You mentioned that Viagra might have an effect on metabolism and blood flow. Is this being studied as a potential additional use of the drug and would it be a gender neutral effect?
BR: Well we all know it helps increase blood flow, and in muscles this could be beneficial. There have been one of two very preliminary studies suggesting that this drug can alter your metabolism and blood flow in a positive way. It would probably be gender neutral in terms of these benefits. The key seems to be that it helps increase muscle perfusion and nutritive flow to muscle cells which may help in the maintenance of muscle mass.
Q: How does rapamycin extend life, while the suppression of mTORC1 signaling adversely affect muscle strength?
BR: This is a big paradox in the field. From what we understand, though, is that when you give the mouse rapamycin it extends their life, but they seem more sedentary. So perhaps the lifespan is extended but it is not resulting in increased activity during the increased lifespan. However, dosage is very important and it might be possible to find the correct dosage that will extend lifespan without adversely affecting muscle strength.
Q: What do you think a professional athlete’s mTOR profile looks like compared to an average individual?
BR: I would think that it wouldn’t look too different. Maybe some slight changes, but we don’t really know. There are not many athletes signing up for scientific studies. However, as an athlete, their protein dietary requirement might be a bit different from normal individuals. They need more protein than the average individual, so a bit more than the 30g at each meal, which isn’t surprising as athletes, in general, eat a much larger amount of calories in a day due to how much they burn in training.
Q: Bed rest has often been prescribed as a treatment, or suggested post-surgery. How is that changing?
BR: We are already trying to change this viewpoint, but it is difficult to change a “standard of care” in the medical field. We are having some success in encouraging more physical activity within certain hospitals and rest homes. For post-surgery individuals, we are trying to encourage getting people out of bed as quickly as possible.
Q: For the older population, what type of physical activity would you prescribe?
BR: All exercise is good, but for those that haven’t been doing much regimented exercise, walking is a good start. We have seen remarkable benefits in muscle strength from just starting to walk regularly. After establishing a regular exercise routine, adding to it with strength training can increase muscle health. Additionally, a good diet with balanced nutrients is important.