Molecular Exercise Physiology

An Introduction

Adam Sharples, Henning Wackerhage, James Morton, Adam P Sharples, James P Morton, Henning Wackerhage

• Publisher: Routledge
• Year: 2022
• ISBN:
  9781351617000
• Edition: 2
• Topic: Ciencias biológicas
• Subtopic: Anatomía y fisiología humanas

Fully revised and expanded, the second edition of Molecular Exercise Physiology offers a student-friendly introduction. It introduces a history documenting the emergence of molecular biology techniques to investigate exercise physiology, the methodology used, exercise genetics and epigenetics, and the molecular mechanisms that lead to adaptation after different types of exercise, with explicit links to outcomes in sport performance, nutrition, physical activity and clinical exercise.

Structured around key topics in sport and exercise science and featuring contributions from pioneering scientists, such as Nobel Prize winners, this edition includes new chapters based on cutting-edge research in epigenetics and muscle memory, satellite cells, exercise in cancer, at altitude, and in hot and cold climates. Chapters include learning objectives, structured guides to further reading, review questions, overviews of work by key researchers and box discussions from important pioneers in the field, making it a complete resource for any molecular exercise physiology course. The book includes cell and molecular biology laboratory methods for dissertation and research projects in molecular exercise physiology and muscle physiology.

This book is essential reading for upper-level undergraduate or postgraduate courses in cellular and molecular exercise physiology and muscle physiology. It is a valuable resource for any student with an advanced interest in exercise physiology in both sport performance and clinical settings.

Chapter One Introduction to molecular exercise physiology

Adam P. Sharples and Henning Wackerhage

DOI: 10.4324/9781315110752-1

Introduction

‘Molecular exercise physiology’ is a discipline within exercise physiology and a shortened version of the term ‘molecular and cellular exercise physiology’ which was used, amongst others, by Frank W. Booth (1), a pioneer in this area (see Box 1.1). In the first part of this chapter, we define molecular exercise physiology, distinguish it from exercise biochemistry and trace its roots in molecular biology and exercise physiology.

Box 1.1 Frank W Booth: the advent of molecular biology techniques in exercise physiology

A brief history of a pioneering early scientist in molecular biology of physical inactivity and exercise. Prof. Dr. Frank W Booth was a leading pioneer in using molecular biology to study mechanisms underlying exercise responses and adaptation.

My philosophy of science has evolved under a number of teachings. A conundrum I often ponder is do men make history or does history make men? From my viewpoint, this thought-provoking phrase is a truncated tribute to Karl Marx who wrote, ‘Men make their own history, but they do not make it as they please, they do not make it on their self-selected circumstances, but on their circumstances existing already, given and transmitted from the past’. Certainly, circumstances throughout my training and career have guided my philosophical evolution, but I can’t deny that genes play an important role as well. I started liberal arts at Denison University with an intent to pursue law. Circumstances led me elsewhere. My biology classes gripped my attention. Serendipity had my University begin a swim team in my sophomore year (the only way I could have made the squad), and the assistant swim coach, Robert Haubrich, was also my academic biology advisor. My senior paper required for biology majors in 1964 was on adaptations to exercise. Two events occurred together: (1) My applications to medical school were not successful so I had to look at an alternative, and (2) Professor Haubrich gave me a flyer about a new exercise physiology PhD programme under Charles Tipton at the University of Iowa. I got on a train from Columbus, Ohio and went to Iowa City to view the exercise physiology programme, whose described course of study had intrigued my interest so much that I decided to visit and eventually enter in 1965, to replace my interest in medical school. Other students in the Tipton programme were James Barnard, Ken Baldwin and Ron Terjung. ‘Tip’, a name we respectfully called Charles Tipton, taught me to go after mechanisms and supported my desire to challenge existing dogmas and policies, as this was the period of student discontent over the Vietnam War. University life in the late 1960s was so tremulous with continual protest rallies, and the killing of student protesters at Kent State University, that University administers had to accept student challenges as acceptable on their campus (as opposed to today where minimal protest occurs over the loss of academic freedoms and civil liberties on University campus in response to forced compliance to regulations from the non-democratic, non-elected bureaucrats). Also, during the Cold War period (February 1945–August 1991), the Russians, on 4 October 1957, launched Sputnik I, an orbiting satellite that greatly accentuated the continual threat that the U.S. feared from the Soviet Union. The same rocket that launched Sputnik could send a nuclear warhead anywhere in the world in a matter of minutes (as I saw in the fictional classic 1964 movie Dr. Strangelove or: How I Learned to Stop Worrying and Love the Bomb, which showed a nuclear holocaust from an insane general, in an insanely funny comedy). In 1958, the U.S. Congress passed the National Defense Education Act, whose outgrowth funded Tip’s exercise physiology programme, and my graduate student salary. Russia and the U.S. were in a space race. The first human walk on the moon in 1969 was from the U.S., which further fuelled my interest to the physiological effects of lack of gravity (physical inactivity), along with Jere Mitchell’s and Bengt Saltin’s classic Dallas bedrest study published in the journal Circulation in 1968, and fostered my decision to take a first post-doc at the School of Aerospace Medicine. John Holloszy’s 1967 paper on the biochemical adaptations of exercise led me to my second post-doc experience to join Baldwin and Terjung at John’s lab, a time during which John taught me critical thinking. After finishing my work with Holloszy, I had a choice of two faculty positions in medical schools (Wayne State in Detroit, or the new University of Texas Medical School at Houston). I selected the latter because it was the home of NASA. Soon after arriving in Houston in 1975, molecular biology was coming to the forefront. I saw the potential of explaining inactivity mechanisms in terms of genes. In the early 1980s, I was fortunate to be present when molecular biology began to appear as a tool in biology at the University of Texas Medical School in the Texas Medical Center. Baylor College of Medicine was one block from my medical school, and I listened to many seminars at Baylor during which I began to connect molecular techniques with my research in exercise and inactivity. My first grad student, Peter Watson, collaborated with Joe Stein in biochemistry and endocrinology, whose lab was just a few doors down from mine, to measure mRNAs. We used dot-blot hybridization of P32-labelled plasmids containing the skeletal muscle alpha-actin cDNA in isolated RNA on a nitrocellulose membrane and published the work in the American Journal of Physiology in 1984. Concurrently, in 1980, Kary Mullis invented the PCR, a method for multiplying DNA sequences in-vitro, and I began using this technique when it became commercialized.

I will end with where I started: Do humans make history or does history make humans perform some event? I think it is both, like gene–environment interaction determining phenotype. History and human curiosity interact to determine how well scientific understanding can explain why physical inactivity is an actual contributor to chronic disease and longevity. As Robert Frost, Pulitzer Prize for Poetry, United States Poet Laureate, ended his poem ‘Stopping by Woods on a Snowy Evening’:

• The woods are lovely, dark and deep.
• But I have promises to keep,
• And miles to go before I sleep,
• And miles to go before I sleep.

So my journey of life continues, as I have miles and miles to go before I sleep.

Frank Booth, University of Missouri, August, 2013

Origins and definition of molecular exercise physiology

We define molecular exercise physiology as ‘the study of the molecular responses to exercise and underlying mechanisms that lead to physiological adaptation following exercise’. The field is focused particularly at the level of the molecule and cell, and investigates how the microscopic make-up of our cells responds to exercise, ultimately leading to adaptation at the cellular, tissue and system levels. The discipline combines the use of molecular biology wet-laboratory techniques with physiological methods to examine the molecular make-up and responses of our cells and tissues to exercise. Therefore, molecular exercise physiologists are concerned with four overarching areas of study: (1) The role of heritable genetic traits (variation in the genetic code found within our DNA) and their associated influence on the physiological response and adaptation to exercise. More recently with a sharper focus on the role of (2) ‘epi’-genetics (meaning ‘above’ genetics), where both the environmental ‘stressor’ of exercise and underlying genetics interact to influence molecular responses and adaptation to exercise, for example, by molecular modifications to our genetic code at the DNA level that subsequently affect how our genes are turned on and off following exercise. In terms of the molecular responses to exercise, exercise physiologists also want to understand: (3) How the environmental ‘stressor’ of exercise modulates the abundance and activity of molecular ‘signal-transduction’ networks, leading to the turning on or off of genes and therefore the resulting protein levels, culminating in changes/adaptation at the cellular or tissue level. Of course, these molecular mechanisms are also applicable across other exercise physiology sub-disciplines, such as sports and exercise nutrition, different environmental conditions (e.g. hot, cold conditions, at altitude and different time zones), ageing and diseases (e.g. cancer, diabetes and obesity). Therefore, molecular exercise physiology has diversified rapidly to incorporate the use of molecular biology to study exercise in aligned sport and exercise fields across performance and health-related disciplines. The majority of these regulatory and molecular mechanisms are studied in blood and skeletal muscle tissue and/or isolated satellite cells (regenerative cell found in skeletal muscle) and sometimes adipose tissue, albeit to a lesser extent than muscle tissue. This is due to the relative ease of sampling of blood and the ever-increasing obtainability of skeletal muscle biopsies in human participants and/or patients under various exercise conditions. Finally, molecular exercise physiologists have also been interested in (4) the role of satellite cells and their role in the repair and regeneration of muscle after exercise, and more recently its role as a molecular ‘communicator’ in skeletal muscle.

Book overview and chapter outline

After providing a short history of the evolution of molecular exercise physiology as a field (Chapter 1), the book will start by introducing the main methods (Chapter 2) employed by molecular exercise physiologists. This will provide an important understanding of the main methods that are employed in the research that is then discussed in the later theoretical chapters. Chapter 3 will introduce sport and exercise genetics and the ‘central dogma’ of molecular biology, DNA to RNA to protein, and how this relates to exercise physiology. Importantly, it will cover how variations in inherited information found in our genetic code may contribute to changes in physiology that could affect exercise and physiological performance. Chapter 4 will then discuss the genetics of muscle mass and strength, and in Chapter 5, we go on to cover the genetics of endurance exercise. Chapter 6 will discuss how exercise can ‘epigenetically’ modify our inherited genetic code and lead to altered molecular responses involved in exercise adaptation. Because epigenetic modifications to DNA can be retained over longer periods, this chapter w...