Insights into how muscle adapts to endurance

Duke University Medical Center researchers have identified the skeletal muscle changes that occur in response to endurance exercise and have better defined the role of vascular endothelial growth factor (VEGF) in creating new blood vessels, known as angiogenesis, in the process.

VEGF is a protein known to trigger blood vessel growth by activating numerous genes involved in angiogenesis.

The researchers’ new insights could provide a roadmap for medical investigators as they seek to use VEGF in treating human conditions characterized by lack of adequate blood flow, such as coronary artery disease or peripheral arterial disease.

Using mice as animal models, the researchers found that exercise initially stimulates the production of VEGF, which then leads to an increase in the number of capillaries within a specific muscle fiber type, ultimately leading to an anaerobic to aerobic change in the muscle fibers supplied by those vessels. The VEGF gene produces a protein that is known to trigger blood vessel growth.

The results of the Duke experiments were presented by cardiologist Richard Waters, M.D., Nov. 8, 2004, at the American Heart Association’s annual scientific sessions in New Orleans.

“It is known that exercise can improve the symptoms of peripheral arterial disease in humans and it has been assumed that angiogenesis played a role in this improvement,” Waters said. “However, the clinical angiogenesis trials to date utilizing VEGF have been marginally successful and largely disappointing, so we felt it would be better at this point to return to animal studies in an attempt to better understand the angiogenic process.”

The Duke team performed their experiments using a mouse model of voluntary exercise. This experimental approach is important, they explained, because most skeletal muscle adaptation studies utilize electrical stimulation of the muscle, which is much less physiologic and does not as closely mimic what would be expected in human exercise.

When placed in the dark with a running wheel, mice will instinctively run, the researchers said. In the Duke experiments, 41 out of 42 mice “ran” up to seven miles each night. At regular intervals over a 28-day period, the researchers then performed detailed analysis of capillary growth and the subsequent changes in muscle fiber type and compared these findings to sedentary mice.

Mammalian muscle is generally made up of two different fiber types – slow-twitch fibers requiring oxygen to function, and the fast-twitch fibers, which function in the absence of oxygen by breaking down glucose. Because of their need for oxygen, slow-twitch fibers tend to have a higher density of capillaries.

“Exercise training is probably the most widely utilized physiological stimulus for skeletal muscle, but the mechanisms underlying the adaptations muscle fibers make in response to exercise is not well understood,” Waters said. “What we have shown in our model is that increases in the capillary density occur before a significant change from fast-twitch to slow-twitch fiber type, and furthermore, that changes in levels of the VEGF protein occur before the increased capillary density.”

“Interestingly, capillary growth appears to occur preferentially among fast-twitch fibers, and it is these very fibers that likely change to slow-twitch fibers,” Waters said. “Since exercise has the potential to impact an enormous number of clinical conditions, therapeutic manipulations intended to alter the response to exercise would benefit from a more detailed understanding of what actually happens to muscle as a result of exercise.”

The exact relationship between VEGF, exercise induced angiogenesis, and muscle fiber type adaptation is still not clear and will become the focus of the group’s continuing research. The findings from the current study, however, are providing important temporal and spatial clues to the adaptability process.

“Our data suggests that angiogenesis is one of the key early steps in skeletal muscle adaptation and may be an essential step in the adaptability process,” Waters continued. “This understanding could be crucial for designing new studies that can be performed to inhibit the angiogenic response to exercise in order to directly test the links between angiogenesis and skeletal muscle plasticity.”

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The research team was supported by grants from the American Heart Association and the U.S. Department of Veterans Affairs.

Other members of the Duke team were Ping Li, Brian Annex, M.D., and Zhen Yan, Ph.D. Svein Rotevatn, Haukeland University Hospital, Bergen, Norway, was also a member of the team.

Duke University Medical Center researchers have identified the skeletal muscle changes that occur in response to endurance exercise and have better defined the role of vascular endothelial growth factor (VEGF) in creating new blood vessels, known as angiogenesis, in the process.

VEGF is a protein known to trigger blood vessel growth by activating numerous genes involved in angiogenesis.

The researchers’ new insights could provide a roadmap for medical investigators as they seek to use VEGF in treating human conditions characterized by lack of adequate blood flow, such as coronary artery disease or peripheral arterial disease.

Using mice as animal models, the researchers found that exercise initially stimulates the production of VEGF, which then leads to an increase in the number of capillaries within a specific muscle fiber type, ultimately leading to an anaerobic to aerobic change in the muscle fibers supplied by those vessels. The VEGF gene produces a protein that is known to trigger blood vessel growth.

The results of the Duke experiments were presented by cardiologist Richard Waters, M.D., Nov. 8, 2004, at the American Heart Association’s annual scientific sessions in New Orleans.

“It is known that exercise can improve the symptoms of peripheral arterial disease in humans and it has been assumed that angiogenesis played a role in this improvement,” Waters said. “However, the clinical angiogenesis trials to date utilizing VEGF have been marginally successful and largely disappointing, so we felt it would be better at this point to return to animal studies in an attempt to better understand the angiogenic process.”

The Duke team performed their experiments using a mouse model of voluntary exercise. This experimental approach is important, they explained, because most skeletal muscle adaptation studies utilize electrical stimulation of the muscle, which is much less physiologic and does not as closely mimic what would be expected in human exercise.

When placed in the dark with a running wheel, mice will instinctively run, the researchers said. In the Duke experiments, 41 out of 42 mice “ran” up to seven miles each night. At regular intervals over a 28-day period, the researchers then performed detailed analysis of capillary growth and the subsequent changes in muscle fiber type and compared these findings to sedentary mice.

Mammalian muscle is generally made up of two different fiber types – slow-twitch fibers requiring oxygen to function, and the fast-twitch fibers, which function in the absence of oxygen by breaking down glucose. Because of their need for oxygen, slow-twitch fibers tend to have a higher density of capillaries.

“Exercise training is probably the most widely utilized physiological stimulus for skeletal muscle, but the mechanisms underlying the adaptations muscle fibers make in response to exercise is not well understood,” Waters said. “What we have shown in our model is that increases in the capillary density occur before a significant change from fast-twitch to slow-twitch fiber type, and furthermore, that changes in levels of the VEGF protein occur before the increased capillary density.”

“Interestingly, capillary growth appears to occur preferentially among fast-twitch fibers, and it is these very fibers that likely change to slow-twitch fibers,” Waters said. “Since exercise has the potential to impact an enormous number of clinical conditions, therapeutic manipulations intended to alter the response to exercise would benefit from a more detailed understanding of what actually happens to muscle as a result of exercise.”

The exact relationship between VEGF, exercise induced angiogenesis, and muscle fiber type adaptation is still not clear and will become the focus of the group’s continuing research. The findings from the current study, however, are providing important temporal and spatial clues to the adaptability process.

“Our data suggests that angiogenesis is one of the key early steps in skeletal muscle adaptation and may be an essential step in the adaptability process,” Waters continued. “This understanding could be crucial for designing new studies that can be performed to inhibit the angiogenic response to exercise in order to directly test the links between angiogenesis and skeletal muscle plasticity.”

 

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Article adapted by MD Sports from original press release.
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Contact: Richard Merritt
Duke University Medical Center 

The research team was supported by grants from the American Heart Association and the U.S. Department of Veterans Affairs

Cereal and Milk Good for Exercise Muscle Recovery

Cereal and non-fat milk is as good as a commercially-available sports drink in initiating post-exercise muscle recovery.

Background

This study compared the effects of ingesting cereal and nonfat milk (Cereal) and a carbohydrate-electrolyte sports drink (Drink) immediately following endurance exercise on muscle glycogen synthesis and the phosphorylation state of proteins controlling protein synthesis: Akt, mTOR, rpS6 and eIF4E.

Methods

Trained cyclists or triathletes (8 male: 28.0+/-1.6 yrs, 1.8+/-0.0 m, 75.4+/-3.2 kg, 61.0+/-1.6 ml O2 * kg-1 * min-1; 4 female: 25.3+/-1.7 yrs, 1.7+/-0.0 m, 66.9+/-4.6 kg, 46.4+/-1.2 mlO2 * kg-1 * min-1) completed two randomly-ordered trials serving as their own controls. After 2 hours of cycling at 60-65% VO2MAX, a biopsy from the vastus lateralis was obtained (Post0), then subjects consumed either Drink (78.5 g carbohydrate) or Cereal (77 g carbohydrate, 19.5 g protein and 2.7 g fat). Blood was drawn before and at the end of exercise, and at 15, 30 and 60 minutes after treatment. A second biopsy was taken 60 minutes after supplementation (Post60). Differences within and between treatments were tested using repeated measures ANOVA.

Results

At Post60, blood glucose was similar between treatments (Drink 6.1+/-0.3, Cereal 5.6+/-0.2 mmol/L, p<.05), but after Cereal, plasma insulin was significantly higher (Drink 123.1+/-11.8, Cereal 191.0+/-12.3 pmol/L, p<.05), and plasma lactate significantly lower (Drink 1.4+/-0.1, Cereal 1.00+/-0.1 mmol/L, p<.05). Except for higher phosphorylation of mTOR after Cereal, glycogen and muscle proteins were not statistically different between treatments. Significant Post0 to Post60 changes occurred in glycogen (Drink 52.4+/-7.0 to 58.6+/-6.9, Cereal 58.7+/-9.6 to 66.0+/-10.0 mumol/g, p<.05) and rpS6 (Drink 17.9+/-2.5 to 35.2+/-4.9, Cereal 18.6+/-2.2 to 35.4+/-4.4 %Std, p<.05) for each treatment, but only Cereal significantly affected glycogen synthase (Drink 66.6+/-6.9 to 64.9+/-6.9, Cereal 61.1+/-8.0 to 54.2+/-7.2%Std, p<.05), Akt (Drink 57.9+/-3.2 to 55.7+/-3.1, Cereal 53.2+/-4.1 to 60.5+/-3.7 %Std, p<.05) and mTOR (Drink 28.7+/-4.4 to 35.4+/-4.5, Cereal 23.0+/-3.1 to 42.2+/-2.5 %Std, p<.05). eIF4E was unchanged after both treatments.

Conclusion

These results suggest that Cereal is as good as a commercially-available sports drink in initiating post-exercise muscle recovery.

Author: Lynne Kammer, Zhenping Ding, Bei Wang, Daiske Hara, Yi-Hung Liao and John L. Ivy

Credits/Source: Journal of the International Society of Sports Nutrition 2009, 6:11

Athletes’ Improve Performance with Extra Sleep

WESTCHESTER, Ill. – Athletes who get an extra amount of sleep are more likely to improve their performance in a game, according to a research abstract presented at the 21st Annual Meeting of the Associated Professional Sleep Societies (APSS).

The study, authored by Cheri Mah of Stanford University, was conducted on six healthy students on the Stanford men’s basketball team, who maintained their typical sleep-wake patterns for a two-week baseline followed by an extended sleep period in which they obtained as much extra sleep as possible. To assess improvements in athletic performance, the students were judged based on their sprint time and shooting percentages.

Significant improvements in athletic performance were observed, including faster sprint time and increased free-throws. Athletes also reported increased energy and improved mood during practices and games, as well as a decreased level of fatigue.

“Although much research has established the detrimental effects of sleep deprivation on cognitive function, mood and performance, relatively little research has investigated the effects of extra sleep over multiple nights on these variables, and even less on the specific relationship between extra sleep and athletic performance. This study illuminated this latter relationship and showed that obtaining extra sleep was associated with improvements in indicators of athletic performance and mood among members of the men’s basketball team.”

The amount of sleep a person gets affects his or her physical health, emotional well-being, mental abilities, productivity and performance. Recent studies associate lack of sleep with serious health problems such as an increased risk of depression, obesity, cardiovascular disease and diabetes.
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Article adapted by MD Sports from original press release.
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Contact: Jim Arcuri
American Academy of Sleep Medicine 

Experts recommend that adults get between seven and eight hours of sleep each night to maintain good health and optimum performance.

Persons who think they might be suffering from a sleep disorder are encouraged to consult with their primary care physician, who will refer them to a sleep specialist.

The annual SLEEP meeting brings together an international body of 5,000 leading researchers and clinicians in the field of sleep medicine to present and discuss new findings and medical developments related to sleep and sleep disorders.

More than 1,000 research abstracts will be presented at the SLEEP meeting, a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society. The four-day scientific meeting will bring to light new findings that enhance the understanding of the processes of sleep and aid the diagnosis and treatment of sleep disorders such as insomnia, narcolepsy and sleep apnea.

Caffeine taken with carbohydrates increase muscle energy 66%

Recipe to recover more quickly from exercise: Finish workout, eat pasta, and wash down with five or six cups of strong coffee.

Glycogen, the muscle’s primary fuel source during exercise, is replenished more rapidly when athletes ingest both carbohydrate and caffeine following exhaustive exercise, new research from the online edition of the Journal of Applied Physiology shows. Athletes who ingested caffeine with carbohydrate had 66% more glycogen in their muscles four hours after finishing intense, glycogen-depleting exercise, compared to when they consumed carbohydrate alone, according to the study, published by The American Physiological Society.

The study, “High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is co-ingested with caffeine,” is by David J. Pedersen, Sarah J. Lessard, Vernon G. Coffey, Emmanuel G. Churchley, Andrew M. Wootton, They Ng, Matthew J. Watt and John A. Hawley. Dr. Pedersen is with the Garvan Institute of Medical Research in Sydney, Australia, Dr. Watt is from St. Vincent’s Institute of Medical Research, Fitzroy, Victoria, Australia. All others are with the Royal Melbourne Institute of Technology University (RMIT) in Bundoora, Victoria, Australia.

A fuller audio interview with Dr. Hawley is available in Episode 11 of the APS podcast, Life Lines, at www.lifelines.tv. The show also includes an interview with Dr. Stanley Schultz, whose physiological discovery of how sugar is transported in the gut led to the development of oral rehydration therapy and sports drinks such as Gatorade and Hi-5.

Caffeine aids carbohydrate uptake  

It is already established that consuming carbohydrate and caffeine prior to and during exercise improves a variety of athletic performances. This is the first study to show that caffeine combined with carbohydrates following exercise can help refuel the muscle faster.

“If you have 66% more fuel for the next day’s training or competition, there is absolutely no question you will go farther or faster,” said Dr. Hawley, the study’s senior author. Caffeine is present in common foods and beverages, including coffee, tea, chocolate and cola drinks.

The study was conducted on seven well-trained endurance cyclists who participated in four sessions. The participants first rode a cycle ergometer until exhaustion, and then consumed a low-carbohydrate dinner before going home. This exercise bout was designed to reduce the athletes’ muscle glycogen stores prior to the experimental trial the next day.

The athletes did not eat again until they returned to the lab the next day for the second session when they again cycled until exhaustion. They then ingested a drink that contained carbohydrate alone or carbohydrate plus caffeine and rested in the laboratory for four hours. During this post-exercise rest time, the researchers took several muscle biopsies and multiple blood samples to measure the amount of glycogen being replenished in the muscle, along with the concentrations of glucose-regulating metabolites and hormones in the blood, including glucose and insulin.

The entire two-session process was repeated 7-10 days later. The only difference was that this time, the athletes drank the beverage that they had not consumed in the previous trial. (That is, if they drank the carbohydrate alone in the first trial, they drank the carbohydrate plus caffeine in the second trial, and vice versa.)

The drinks looked, smelled and tasted the same and both contained the same amount of carbohydrate. Neither the researchers nor the cyclists knew which regimen they were receiving, making it a double-blind, placebo-controlled experiment.

Glucose and insulin levels higher with caffeine ingestion

The researchers found the following:  

• one hour after exercise, muscle glycogen levels had replenished to the same extent whether or not the athlete had the drink containing carbohydrate and caffeine or carbohydrate only
• four hours after exercise, the drink containing caffeine resulted in 66% higher glycogen levels compared to the carbohydrate-only drink
• throughout the four-hour recovery period, the caffeinated drink resulted in higher levels of blood glucose and plasma insulin
• several signaling proteins believed to play a role in glucose transport into the muscle were elevated to a greater extent after the athletes ingested the carbohydrate-plus-caffeine drink, compared to the carbohydrate-only drink

 Dr. Hawley said it is not yet clear how caffeine aids in facilitating glucose uptake from the blood into the muscles. However, the higher circulating blood glucose and plasma insulin levels were likely to be a factor. In addition, caffeine may increase the activity of several signaling enzymes, including the calcium-dependent protein kinase and protein kinase B (also called Akt), which have roles in muscle glucose uptake during and after exercise.

Lower dose is next step  

In this study, the researchers used a high dose of caffeine to establish that it could help the muscles convert ingested carbohydrates to glycogen more rapidly. However, because caffeine can have potentially negative effects, such as disturbing sleep or causing jitteriness, the next step is to determine whether smaller doses could accomplish the same goal.

Hawley pointed out that the responses to caffeine ingestion vary widely between individuals. Indeed, while several of the athletes in the study said they had a difficult time sleeping the night after the trial in which they ingested caffeine (8 mg per kilogram of body weight, the equivalent of drinking 5-6 cups of strong coffee), several others fell asleep during the recovery period and reported no adverse effects.

Athletes who want to incorporate caffeine into their workouts should experiment during training sessions well in advance of an important competition to find out what works for them.

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Article adapted by MD Sports from original press release.
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Contact: Christine Guilfoy
American Physiological Society

Physiology is the study of how molecules, cells, tissues and organs function to create health or disease. The American Physiological Society (APS) has been an integral part of this scientific discovery process since it was established in 1887.

G-Trainer: Low-gravity training machine reduces joint and muscle discomfort

A University of Colorado at Boulder study of a space-age, low-gravity training machine used by several 2008 Olympic runners showed it reduced impacts on muscles and joints by nearly half when subjects ran at the equivalent of 50 percent of their body weight.

The new study has implications for both competitive runners rehabilitating from injuries and for ordinary people returning from knee and hip surgeries, according to Associate Professor Rodger Kram of CU-Boulder’s integrative physiology department.

Known as the “G-Trainer,” the machine consists of a treadmill surrounded by an inflatable plastic chamber that encases the lower body of the runner, said Kram. Air pumped into the chamber increases the pressure and effectively reduces the weight of runners, who are sealed in the machine at the waist in a donut-shaped device with a special zipper and “literally lifted up by their padded neoprene shorts,” he said.

Published in the August issue of the Journal of Applied Biomechanics, the study is the first to quantify the effects of running in the G-Trainer, built by Alter-G Inc. of Menlo Park, Calif., using technology developed at NASA’s Ames Research Center in California. The paper was authored by Kram and former CU-Boulder doctoral student Alena Grabowski, now a postdoctoral researcher at the Massachusetts Institute of Technology.

Although G-Trainers have been used in some sports clinics and college and professional sports training rooms since 2006, the new study is the first scientific analysis of the device as a training tool for running, said Grabowski.

“The idea was to measure which levels of weight support and speeds give us the best combination of aerobic workout while reducing the impact on joints,” said Kram. “We showed that a person can run faster in the G-Trainer at a lower weight and still get substantial aerobic benefits while maintaining good neuromuscular coordination.”

The results indicated a subject running at the equivalent of half their weight in the G-Trainer at about 10 feet per second, for example — the equivalent of a seven-minute mile — decreased the “peak” force resulting from heel impact by 44 percent, said Grabowski. That is important, she said, because each foot impact at high speed can jar the body with a force equal to twice a runner’s weight.

Several former CU track athletes participating in the 2008 Olympics in Beijing have used the machine, said Kram. Alumna Kara Goucher, who will be running the 5,000- and 10,000-meter races in Beijing, has used the one in Kram’s CU-Boulder lab and one in Eugene, Ore., for rehabilitation, and former CU All-American and Olympic marathoner Dathan Ritzenhein also uses a G-Trainer in his home in Oregon. Other current CU track athletes who have been injured have tried the machine in Kram’s lab and found it helpful to maintain their fitness as they recovered, Kram said.

For the study, the researchers retrofitted the G-Trainer with a force-measuring treadmill invented by Kram’s team that charts vertical and horizontal stress load on each foot during locomotion, measuring the variation of biomechanical forces on the legs during running. Ten subjects each ran at three different speeds at various reduced weights, with each run lasting seven minutes. The researchers also measured oxygen consumption during each test, Kram said.

Grabowski likened the effect of the G-Trainer on a runner to pressurized air pushing on the cork of a bottle. “If you can decrease the intensity of these peak forces during running, then you probably will decrease the risk of injury to the runner.”

The G-Trainer is a spinoff of technology originally developed by Rob Whalen, who conceived the idea while working at NASA Ames as a National Research Council fellow to help astronauts maintain fitness during prolonged space flight. While the NASA technology was designed to effectively increase the weight of the astronauts to stem muscle atrophy and bone loss in low-gravity conditions, the G-Trainer reverses the process, said Grabowski.

In the past, sports trainers and researchers have used climbing harnesses over treadmills or flotation devices in deep-water swimming pools to help support the weight of subjects, said Kram. Harnesses are cumbersome, while pool exercises don’t provide sufficient aerobic stimulation and biomechanical loading on the legs, he said.

Marathon world-record holder Paula Radcliffe of Great Britain is currently using a G-Trainer in her high-altitude training base in Font-Remeu, France. Radcliffe is trying to stay in top running shape while recovering from a stress fracture in her femur in time for the 2008 Olympic women’s marathon on Aug. 17, according to the London Telegraph.

Kram and Grabowski have begun a follow-up study of walking using the G-Trainer. By studying subjects walking at various weights and speeds in the machine, the researchers should be able to quantify its effectiveness as a rehabilitation device for people recovering from surgeries, stress fractures and other lower body injuries, Kram said.

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Article adapted by MD Sports from original press release.
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Contact: Rodger Kram
University of Colorado at Boulder

New exercise gene stops depression

Boosting an exercise-related gene in the brain works as a powerful anti-depressant in mice—a finding that could lead to a new anti-depressant drug target, according to a Yale School of Medicine report in Nature Medicine.

“The VGF exercise-related gene and target for drug development could be even better than chemical antidepressants because it is already present in the brain,” said Ronald Duman, professor of psychiatry and senior author of the study.

Depression affects 16 percent of the population in the United States, at a related cost of $83 billion each year. Currently available anti-depressants help 65 percent of patients and require weeks to months before the patients experience relief.

Duman said it is known that exercise improves brain function and mental health, and provides protective benefits in the event of a brain injury or disease, but how this all happens in the brain is not well understood. He said the fact that existing medications take so long to work indicates that some neuronal adaptation or plasticity is needed.

He and his colleagues designed a custom microarray that was optimized to show small changes in gene expression, particularly in the brain’s hippocampus, a limbic structure highly sensitive to stress hormones, depression, and anti-depressants.

They then compared the brain activity of sedentary mice to those who were given running wheels. The researchers observed that the mice with wheels within one week were running more than six miles each night. Four independent array analyses of the mice turned up 33 hippocampal exercise-regulated genes—27 of which had never been identified before.

The action of one gene in particular—VGF—was greatly enhanced by exercise. Moreover, administering VGF functioned like a powerful anti-depressant, while blocking VGF inhibited the effects of exercise and induced depressive-like behavior in the mice.

“Identification of VGF provides a mechanism by which exercise produces antidepressant effects,” Duman said. “This information further supports the benefits of exercise and provides a novel target for the development of new antidepressants with a completely different mechanism of action than existing medications.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: Jacqueline Weaver
Yale University
Nature Medicine

Exercise Pill Dramatically Increases Endurance

Trying to reap the health benefits of exercise? Forget treadmills and spin classes, researchers at the Salk Institute for Biological Studies may have found a way around the sweat and pain. They identified two signaling pathways that are activated in response to exercise and converge to dramatically increase endurance.

The team of scientists, led by Howard Hughes Medical Investigator Ronald M. Evans, Ph.D., a professor in the Salk Institute’s Gene Expression Laboratory report in the July 31 advance online edition of the journal Cell that simultaneously triggering both pathways with oral drugs turned laboratory mice into long-distance runners and conferred many of exercise’s other benefits.

In addition to their allure for endurance athletes, drugs that mimic the effects of exercise have therapeutic potential in treating certain muscle diseases, such as wasting and frailty, hospital patients unable to exercise, veterans and others with disabilities as well as obesity and a slew of associated metabolic disorders where exercise is known to be beneficial.

Previous work with genetically engineered mice in the Evans lab had revealed that permanently activating a genetic switch known as PPAR delta turned mice into indefatigable marathon runners. In addition to their super-endurance, the altered mice were resistant to weight gain, even when fed a high-fat diet that caused obesity in ordinary mice. On top of their lean and mean physique, their response to insulin improved, lowering levels of circulating glucose.

“We wanted to know whether a drug specific for PPAR delta would have the same beneficial effects,” says Evans. “Genetic engineering in humans, commonly known as gene doping when mentioned in connection with athletic performance, is certainly feasible but very impractical.”

An investigational drug, identified only as GW1516 (and not commercially available), fit the bill. When postdoctoral researcher and lead author Vihang A. Narkar, Ph.D., fed the substance to laboratory mice over a period of four weeks, the researchers were in for a surprise.

“We got the expected benefits in lowering fatty acids and blood glucose levels but no effect, absolutely none, on exercise performance,” says Narkar. Undeterred, he put mice treated with GW1516 on a regular exercise regimen and every day had them run up to 50 minutes on a treadmill.

Now the exact same drug that had shown no effect in sedentary animals improved endurance by 77 percent over exercise alone and increased the portion of “non-fatiguing” or “slow twitch” muscle fibers by 38 percent. The result, while very dramatic, gave rise to a vexing question: Why is exercise so important?

First and foremost, exercise depletes muscles’ energy store, a chemical known as ATP. In times of high demand, ATP releases all its energy and forms AMP. Rising AMP levels alert AMPK, a metabolic master regulator, which acts like a gas gauge that the cell is running on empty and revs up the production of ATP. “That led us to consider whether AMPK activation was the critical trigger that allowed PPAR delta to work,” recalls Narkar.

Usually, AMPK can be found in the cytoplasm, the compartment that surrounds the nucleus, but the Salk researchers’ experiment revealed that some exercise-activated AMPK molecules slip into the nucleus. There they physically interact with PPAR delta and increase its ability to turn on the genetic network that increases endurance.

“It essentially puts a turbo charge on PPAR delta, which explains why exercise is so important,” says Evans.

Then came the ultimate couch potato experiment. The researchers fed untrained mice AICAR, a synthetic AMP analog that directly activates AMPK. After only four weeks and without any prior training, these mice got up and ran 44 percent longer than untreated, untrained mice. “That’s as much improvement as we get with regular exercise,” says Narkar.

“Exercise in a pill” might sound tempting to couch potatoes and Olympic contenders alike, but the dreams of the latter might be cut short. Evans developed a test that can readily detect GW1516 and its metabolites as well as AICAR in blood and urine and is already working with officials at the World Anti-Doping Association, who are racing to have a test in place in time for this year’s Summer Olympics.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Gina Kirchweger
Salk Institute

The study was supported by the Howard Hughes Medical Institute, the Hillblom Foundation and the National Institute of Health.

Researchers who contributed to the work include postdoctoral researchers Michael Downes, Ph.D., Ruth T. Yu, Ph.D., doctoral candidate Emi Embler, B.S., research associates Michael C. Nelson, B.S., Yuhua Zou, M.S., Ester Banayo, and Henry Juguilon, in the Gene Expression Laboratory, doctoral candidate M. Mihaylova, and assistant professor Reuben Shaw, Ph.D., in the Molecular and Cell Biology Laboratory, assistant professor Yong-Xu Wang, Ph.D., at the University of Massachusetts Medical School, Massachusetts, and professor Heonjoon Kang, Ph.D., at the School of Earth and Environmental Sciences, Seoul National University, South Korea.

Low-Fat Diet Hurts Runners Perfomance, Suppresses Immune Function, and Increases Infection Risk

Trained runners who severely limit the amount of fat in their diets may be suppressing their immune system and increasing their susceptibility to infections and inflammation, a University at Buffalo study has shown.In findings presented here today (May 22, 1999) at the fourth International Society for Exercise and Immunology Symposium, lead author Jaya T. Venkatraman, Ph.D., reported that running 40 miles per week on a diet composed of approximately 17 percent fat compromised the runners’ immune response.

The medium and high-fat diets, composed of approximately 32 and 41 percent fat respectively, left the immune system intact, and enhanced certain components, the findings showed.

“The data suggest that higher-fat diets may lower the proinflammatory cytokines, free radicals and hormones, and may enhance the levels of anti-inflammatory cytokines,” Venkatraman said.

Venkatraman is an associate professor of nutrition in the Department of Physical Therapy, Exercise and Nutrition Sciences in the UB School of Health Related Professions.

Earlier studies published by a UB research group headed by David Pendergast, Ed.D., professor of physiology and biophysics, reported that competitive runners who increased the proportion of fat in their diets improved their endurance with no negative effect on weight, body composition, blood pressure, pulse rate or total cholesterol. (See editor’s note)

However, since a high level of fat was thought to be immunosuppressive, the researchers sought to determine if increasing dietary fat would compromise various elements of the immune system, while improving performance.

“In general, moderate levels of exercise are known to enhance the immune system,” said Venkatraman. “But high-intensity exercise and endurance exercise produce excess levels of free radicals, which may place stress on the immune system.

“Since we have shown that athletes perform better on a higher-fat diet than on a low-fat diet, it was important to determine if the higher-fat diet would further compromise the immune system,” she said. “We found that it did not, but the very-low-fat diet did.”

The study involved six female and eight male competitive runners who trained at 40 miles a week and were part of a larger performance study. They spent a month on their normal diets, followed by a month each on diets composed of approximately 17 percent, 32 percent and 41 percent fat. Protein remained stable at 15 percent and carbohydrates made up the difference.

The immune status of the runners was obtained by analyzing concentrations of essential components of the immune system — leukocytes, cytokines and plasma cortisol — in blood samples taken before and after an endurance exercise test. The tests were conducted at the end of each four-week diet period.

Results showed that natural killer cells, a type of leukocyte and one of the body’s defense mechanisms marshaled to fight infection, were more than doubled in runners after the high-fat diet, compared to the low-fat regimen. Levels of PGE2, inflammation-causing prostaglandins, increased after the endurance test and were higher when the runners were on the low-fat diet.

This study is part of a larger investigation to determine the effects of dietary fat on performance, biochemical and nutritional status, and plasma lipids and lipoprotein profiles in distance runners being conducted by a study group composed of — in addition to Venkatraman and Pendergast — Peter Horvath, Ph.D., associate professor in the UB Department of Physical Therapy, Exercise and Nutrition Sciences, and John Leddy, M.D., clinical professor of orthopaedics and associate director of the UB Sports Medicine Institute.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Lois Baker
University at Buffalo

Old runners improve speed faster than younger runners

Marathon runners 50 and older, and female athletes in particular, are showing greater improvement in running times than younger runners, according to a study by a Yale professor.Peter Jokl, M.D., professor of orthopedics, and his co-authors, Paul Sethi, M.D., and Andrew Cooper, all of Yale School of Medicine, looked at the running time, age, and gender of all of the runners in the New York City Marathon from 1983 through 1999. They also evaluated the performances of the top 50 male and top 50 female finishers by age categories. There were 415,000 runners in all. Master athletes were classified as those 50 and older.

Jokl said women marathon runners 50-59 improved their average race time by 2.08 minutes per year, which was substantially greater than men runners of the same age, whose running time improved on average about eight seconds per year.

The older male runners, in turn, increased their running time at a much greater rate than younger male runners. The younger runners, male and female ages 20 to 30, did not significantly improve their running times during the period studied. The most significant trends in improved running times noted in the top 50 finishers in the male category occurred in age 60-69 and 70-79, and for women, in ages 50-59 and 60-69.

“Our data reflect the potential for improvement of the general health status of our aging population,” Jokl said. “It is not surprising that the number of participating master athletes continues to rise. There is a general trend towards increasing numbers of our aging population who are in good health and physically able to participate in these types of strenuous competitions.”

He said the performance limits of master athletes appear to be greater than predicted by previous physiologic studies.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Jacqueline Weaver
Yale University

Citation: British Journal of Sports Medicine, Vol. 38: pp 408-412, August 2004

Stunning discovery may make Blood-Doping as easy as washing hair

A stunning discovery by German scientists may make blood doping and the treatment of severe anemia as easy as washing your hair.  

In the October print issue of The FASEB Journal (http://www.fasebj.org/), researchers show that the estimated 100,000 hair follicles on each person’s head have the potential to become erythropoietin (EPO) factories. EPO, the hormone primarily responsible for the creation of red blood cells, is used illegally to enhance athletic performance and is used legally to treat severe anemia associated with kidney failure and chemotherapy.

“The ultimate hope is that we’ll be able to up the production of natural EPO in our hair follicles whenever we need it, safely and at a low cost,” said Ralf Paus, senior author of the study. “Our study also highlights that ancient hormones are engaged in many more activities than conventional medical wisdom has assigned to them.”

Normally, EPO is created and released by the kidneys. When the kidneys fail, or when someone undergoes chemotherapy, this process is disrupted and severe anemia occurs. Today, most people are treated using synthetic EPO to bring red blood cells back to normal levels, but synthetic versions of this hormone are relatively expensive. Blood-doping athletes use synthetic EPO to help their bodies bring red blood cells to above-normal levels. This increased concentration of red blood cells allows the blood to deliver more oxygen to muscles than normal, significantly improving endurance and performance. The major danger in boosting the number of red blood cells above normal is that as the blood thickens with red blood cells, the possibility of heart attack increases.

“This study opens doors to an entirely new approach for treating EPO-related anemia,” said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. “The study also is important because it suggests that there is still much to learn about ‘well known’ processes in the body.”

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Article adapted by MD Sports Weblog from original press release.
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Source: Cody Mooneyhan
Federation of American Societies for Experimental Biology

The FASEB Journal (http://www.fasebj.org/) is published by the Federation of American Societies for Experimental Biology (FASEB) and is consistently ranked among the top three biology journals worldwide by the Institute for Scientific Information. FASEB comprises 21 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances biological science through collaborative advocacy for research policies that promote scientific progress and education and lead to improvements in human health.