Molecular Approaches Breathe New Life Into Sports Medicine

Now that summer is in full swing, all but the most dedicated couch potatoes are playing on departmental softball teams, hitting the tennis courts, or laboring in the garden. For a growing number of scientists, however, exercise is more than a seasonal diversion-it's the focus of a thriving discipline that integrates molecular and cellular biology, physiology, nutrition, and behavioral sciences. One important trend, not only in exercise science but also in physiology, is the integration of molecular and cellular approaches with more holistic studies. "What's really competitive and compelling is research that looks at the entire animal, whether it be a human or a rat, and then integrates that down to the cellular and even molecular level," says Charlotte Tate, a professor of pharmacology at the University of Houston and president of the Indianapolis-based American College of Sports Medicine (ACSM). "For example, how does contractile activity in the muscle turn genes on and off?" Tate's own research focuses on the cellular mechanisms behind the aging heart's ability to improve blood flow in response to exercise. INTEGRATIVE APPROACH: Kenneth Baldwin, a pioneer in the field, notes that successful grantees' research is mechanistic and hypothesis-driven. "Those investigators that can move their research into an integrative biology approach are going to be more successful in getting money from the funding institutions," states Kenneth Baldwin, a professor of physiology and biophysics at the University of California, Irvine. "If your research is not mechanistic and hypothesis-driven, you will have a hard time getting funded." While it's generally acknowledged that exercise scientists have been slow in bringing molecular approaches to their research, that's rapidly changing. Baldwin, along with Frank Booth, a professor of integrative biology, pharmacology, and physiology at the University of Texas, Houston, is generally associated with pioneering the use of molecular techniques in exercise science. "One of the problems that has hindered exercise science is that most of the individuals involved in this research have had to deal with intact animal models or humans," observes Baldwin. For this reason, in vivo systems for studying gene expression such as DNA transfection of skeletal and cardiac muscle cells as well as transgenic mouse models have become invaluable tools for exercise scientists. "We now have animal models that enable an investigator to study how resistance training can cause skeletal muscles to adapt and change their structural and functional properties," Baldwin says. He studies one of the contractile proteins within the muscle, an isoform of myosin that plays a pivotal role in everyday weightbearing activities, and the ways in which its expression is regulated by both hormonal and mechanical factors. It's no secret that exercise is essential for a healthy heart. But scientists are questioning just how intensely people need to exercise to accrue cardiovascular benefits. For years, the dogma was that two or three intense exercise workouts several times a week were necessary for cardiovascular fitness. However, a panel of exercise scientists convened by the Centers for Disease Control and Prevention (CDC) and ACSM in 1993 found that belief to be unfounded. It reported that 30 minutes of moderate exercise, such as walking, gardening, or bicycling, spread out over the course of a day, provided the bulk of cardiovascular benefits. One study used to back up the report was conducted by Steven Blair, director of research at the Cooper Institute for Aerobics Research in Dallas (S.N. Blair et al., JAMA-Journal of the American Medical Association, 262:2395-401, 1989; for a follow-up report, see S.N. Blair et al., JAMA, 276:205-10, 1996). Blair assigned one of three fitness categories-low fit, moderately fit, and high fit-to more than 13,000 men and women based on their performances on a treadmill test. The categories roughly corresponded to levels of physical activity. He observed that those in the least-fit category were the most likely to die over the eight-year course of the study, with the greatest difference in death rates between the low-fit and the moderately fit groups. "You get more bang for your buck, so to speak, by getting out of the low-fit category and into the moderate," says Blair. "If you go from low fit or completely sedentary to moderately fit and moderately active, you can cut your risk of dying by about 50 percent. If you go from moderate to high, I think you can drop your risk by another 10 [percent] to 15 percent." But the CDC/ACSM report has raised the collective blood pressure of some exercise scientists, who maintain that the recent recommendations lack supporting data. One vocal critic, Paul Williams of Lawrence Berkeley National Laboratory in Berkeley, Calif., says that the cardiovascular benefits increase linearly with the intensity of exercise (M. Barinaga, Science, 276:1324-7, 1997). Determining the role of exercise intensity will continue to be a major focus for exercise scientists in the years to come, predicts Blair. Interest in the relationship between exercise and other diseases, particularly cancer and diabetes, is also growing. "Exercise is a physical stressor," states Laurie Hoffman-Goetz, a professor of health studies and gerontology, and of kinesiology at the University of Waterloo. "It may have positive effects, or it may have negative effects, but it's a stressor." Although moderate exercise appears to boost immune function, athletes who overtrain are susceptible to infections. However, animal models show that exercise-induced changes in immune function may slow the spread of metastatic cancer cells. "This is really an area in its infancy," cautions Hoffman-Goetz. "The whole area of exercise immunology has only been around the past 10 years." HOLISTIC STUDIES: J. Mark Davis studies a possible connection between the central nervous system and muscle fatigue. Other researchers are focusing on the interplay of exercise and the central nervous system (CNS). "A lot of us say that in exercise physiology we were studying a headless body," comments J. Mark Davis, a professor of exercise science at the University of South Carolina. "When you understand physiology very well, you understand that the organs of the body just cannot work without control and integration of the nervous system." While phenomena like muscle fatigue have long been recognized by scientists and athletes alike, only recently has there been reason to suspect a CNS connection. "There are many situations," says Davis, "in which we see fatigue that can't necessarily be explained by what's going on in the muscle." One of the molecules Davis suspects is involved in CNS fatigue is serotonin, a neurotransmitter known for its involvement in depression and sleep. THE RACER'S EDGE? Priscilla Clarson notes that the long term consequences of taking high doses of creatine are unknown. Molecular and cellular techniques have also changed research into sport nutrition. The impact of high-fat diets, branched-chain amino acids (leucine, isoleucine, and valine), carnitine, and even hot red chili pepper supplements on athletic performance has garnered recent attention. The two hottest supplements, according to Priscilla Clarkson, a professor of exercise science at the University of Massachusetts, Amherst, and editor of the International Journal of Sport Nutrition, are antioxidants and creatine. Antioxidant supplements have come into use because strenuous physical exercise is often accompanied by an increase in the production of free radicals. Creatine supplements have become popular because creatine phosphate stores in the muscle provide the high-energy phosphate for adenosine diphosphate (ADP) to restore adenosine triphosphate (ATP) levels quickly. American College of Sports Medicine http://www.acsm.org/ American Diabetes Association http://www.diabetes.org:80/default.htm American Heart Association One of the most critical problems in exercise science is simply getting people into the gym. Exercise psychology and sociology are hot research areas, thanks in part to the Surgeon General's 1996 Report on Physical Activity and Health (http://www.cdc.gov/nccdphp/sgr/sgr.htm), which emphasized the need to promote healthier lifestyles in people of all ages. And that translates to better career opportunities for behavioral scientists interested in promoting exercise, according to Barbara Campaigne, ACSM's director of research development. RUNNING CONTROVERSY: A study by Steven Blair finding that moderate exercise provides "the most bang for your buck" has been criticized. "One area that's being funded is research on exercise related to specific populations," says Campaigne. "How do we get minorities, women, and older adults to be more appropriately active? What health behaviors are related? What are ways to encourage individuals to adhere to their exercise regime?" Edward McAuley, a professor of kinesiology at the University of Illinois, Urbana-Champaign, says that 50 percent of people who begin an exercise program drop out within the first six months. "As yet we haven't been entirely successful in coming up with strategies for maintaining long-term exercise behavior." McAuley and his colleagues are in the middle of a large study examining the role of exercise in both the psychological and cognitive functioning of elderly adults. "We think that as people exercise more, they may increase their sense of environmental control and thus improve mental health. The other side is that increased physical fitness may increase blood flow to the brain, perhaps bringing about changes in cognitive function, attention, and memory." Exercise science as a discipline itself is undergoing some fairly radical changes. Exercise science or kinesiology departments once were a part of colleges of education, when they were known as physical education departments and were geared toward training coaches or athletic trainers. Now that exercise science is moving out of schools of education and into science departments, it's gaining acceptance as a rigorous discipline. In recent years, government cutbacks have forced many universities to shut down their exercise science departments, with researchers being absorbed into basic science departments. However, many universities-including the University of Texas; the University of California, Berkeley; the University of Southern California; the University of Michigan; the University of Illinois; Arizona State University; the University of South Carolina; and the University of Florida-continue to maintain strong exercise science or kinesiology departments. The multidisciplinary nature of exercise science is reflected in the literature. Specialty journals, such as Medicine and Science in Sports and Exercise or the American Journal of Sports Medicine, and an increasing number of medical and biological journals are now focusing on exercise science research. According to data from the Philadelphia-based Institute for Scientific Information (ISI), 53 sports medicine journals published 23,354 papers between 1981 and 1996. ISI publishes the Focus On: Sports Science & Medicine database. The multidisciplinary nature of the field also is reflected in the variety of agencies that fund research. The National Institutes of Health funds exercise science. The American Heart Association continues to be a good source of money for cardiovascular research. Emerging interest in the relationship between physical activity and metabolic disorders such as diabetes have led to increased funding from the American Diabetes Association. The National Aeronautics and Space Administration, with its interest in the effects of weightlessness on human physiology and muscle composition, also funds research in exercise science, although ACSM's Tate notes that "it's very competitive." A broad focus is a key for a successful career in exercise science, according to Tate: "My students all have backgrounds in exercise science, but they get their degrees in pharmacology, and so they're qualified to work in a medical school or basic science department. It's important that we become a part of, and not apart from, the mainstream curriculum." Sara Latta is a science writer based in Champaign, Ill.

Molecular Approaches Breathe New Life Into Sports Medicine

Interested in reading more?

Become a Member of