“MIGHTY MOUSE” Gene Increases Muscle Mass in Humans

By studying the genes of a German child born with unusually well developed muscles, an international research team has discovered the first evidence that the gene whose loss makes “mighty mice” also controls muscle growth in people.

Writing in the June 24 issue of the New England Journal of Medicine, German neurologist Markus Schuelke, M.D., and the team show that the child’s extra-large muscles are due to an inherited mutation that effectively silences the myostatin gene, proving that its protein normally keeps muscle development in check in people.

People with muscle-wasting conditions such as muscular dystrophy, and others just wanting to “bulk up,” have eagerly followed work on myostatin, hoping for a way to counteract the protein’s effects in order to build or rebuild muscle mass. But while research with mice has continued to reveal myostatin’s role and the effects of interfering with it, no one knew whether any of the results would be relevant to humans.

“This is the first evidence that myostatin regulates muscle mass in people as it does in other animals,” says Se-Jin Lee, M.D., Ph.D., professor of molecular biology and genetics in the Institute for Basic Biomedical Sciences at Johns Hopkins and co-author on the study. “That gives us a great deal of hope that agents already known to block myostatin activity in mice may be able to increase muscle mass in humans, too.”

Lee and his team discovered in 1997 that knocking out the myostatin gene led to mice that were twice as muscular as their normal siblings, lending them the moniker “mighty mice.” Later, others showed that naturally bulky cattle, such as Belgian Blues, got their extra muscles from lack of myostatin, too.

An unusual opportunity to examine myostatin’s role in humans arose when Schuelke examined a newborn baby boy, almost five years ago, and was struck by the visible muscles on the infant’s upper legs and upper arms. When ultrasound proved that the muscles were roughly twice as large as other infants’, but otherwise normal, Schuelke realized that a naturally occurring mutation in the child’s myostatin gene might be the cause.

Sequencing the myostatin gene from the boy and his mother, who had been a professional athlete, revealed a single change in the building blocks of the gene’s DNA. Surprisingly, the change was not in the gene regions that correspond to the resulting protein, but in the intervening regions that are used only to create protein-making instructions, thus changing the gene’s protein-building message.

“The mutation caused the gene’s message, the messenger RNA, to be wrong,” says Hopkins

neurologist Kathryn Wagner, M.D., Ph.D., who tested the genetic mutation’s effect in laboratory studies. “If the message had been used to make a protein, it would be much shorter than it should be. But we think the process doesn’t even get that far; instead the cells just destroy the message.”

Co-authors from Wyeth Research, Cambridge, Mass., analyzed samples of the child’s blood for evidence of the myostatin protein and found none. “Both copies of the child’s myostatin gene have this mutation, so little if any of the myostatin protein is made,” says Schuelke. “As a result, he has about twice the muscle mass of other children.”

Completely lacking myostatin, the boy is stronger than other children his age, and fortunately has no signs of problems with his heart so far, Schuelke says. But he adds that it’s impossible to know whether the lack of myostatin in that crucial muscle might lead to problems as the boy gets older.

While other family members — the boy’s mother and her brother, father and grandfather — were also reported to have been usually strong, only the mother’s DNA was available for analysis along with her son’s. Schuelke discovered that only one copy of the mother’s myostatin gene had the mutation found in both copies of her son’s myostatin gene. (We have two copies of each gene; one inherited from the mother and one inherited from the father.)

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Article adapted by MD Sports Weblog from original press release.
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 Contact: Joanna Downer
Johns Hopkins Medical Institutions

 

The Johns Hopkins researchers were funded by the National Institutes of Health and the Muscular Dystrophy Association. The German researchers were funded by the parents’ self-help group (Helft dem muskelkranken Kind).

Authors on the paper are Schuekle, Christoph Hubner, Thomas Riebel and Wolfgang Komen of Charite, University Medical Center Berlin, Germany; Wagner and Lee of Johns Hopkins; Leslie Stolz and James Tobin of Wyeth Research, Cambridge, Ma.; and Thomas Braun of Martin-Luther-University, Halle-Wittenberg, Germany.

*Under a licensing agreement between MetaMorphix Inc. and The Johns Hopkins University, Lee is entitled to a share of royalty received by the University on sales of products described in this article. Lee also is entitled to a share of sublicensing income from arrangements between MetaMorphix and American Home Products (Wyeth Ayerst Laboratories) and Cape Aquaculture Technologies. Lee and the University own MetaMorphix Inc. stock, which is subject to certain restrictions under University policy. Lee owns Cape Aquaculture Technologies stock, which is subject to certain restrictions under University policy. Lee has served as a paid consultant to MetaMorphix Inc. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.

Workout Around Injuries, Don’t Stop Working Out

A strained muscle, sprained ankle or foot injury can make even the most motivated exerciser feel discouraged when it comes to working out.

But being injured doesn’t necessarily mean you can’t exercise, says Colleen Greene, wellness coordinator with MFit, the University of Michigan Health System’s health promotion division. By speaking with an expert and finding a plan that will work as you heal, you can still hit the gym while recovering.

“Exercise can definitely be beneficial for a person dealing with an injury. Depending on its type, the injured area should be moved and not left in place for a long period of time,” explains Greene. “Some people think they should just rest and not move at all with an injury. Doing that can actually be worse because—depending on the amount of time one does not move the appendage— the muscle might begin to atrophy.”

Greene notes that the general rule of thumb when initially handling an injury is to follow RICE—Rest, Ice, Compression and Elevation. Once you have done this, consult a doctor to look at the injury as soon as possible. You may be referred to a physical therapist or specialist trainer if the injury is severe enough. These professionals can provide guidance for your recovery, as well as give you tips on how to maintain strength while recovering.  

Greene also notes that there are “dos and don’ts” when it comes to specific injuries. Because each condition is unique, there are certain things a person can do and other activities the injured person should avoid while healing. She offers these tips on three common injuries:

General advice for any injury: See a physician or physical therapist to learn what exercises are possible with your type of injury. Focus on the goal of maintaining strength, not gaining it, while you are recovering. And always be wary of pain as you explore different workouts.

“Pain is always the indicator; discomfort is OK, but pain tells you when you should stop what you are doing and do something else,” Greene says. “You always want to keep in mind that you should be doing something that doesn’t re-injure or further injure yourself.”

Sprained ankle. When seeking out cardiovascular exercises, Greene suggests sticking with low- impact workouts, such as swimming or riding a stationary bike. She notes that running or aerobics are generally activities that are too high in impact. A person with a sprained ankle can also do upper-body or core impact exercises for strength training.

Plantar faciitis. Plantar faciitis is an overuse injury normally caused by a lack of cross training. For example, a person may develop plantar faciitis by only running when training for a marathon, but not preparing through other exercises, such as swimming or biking. Greene notes that people dealing with this type of injury need to focus on resting in order to heal, but it is possible to explore low-impact core and upper-body exercises while recovering.

“There are not a lot of ways other than physical therapy to recover from plantar faciitis except for resting,” she says. “You want to do things that are low impact without a lot of pressure on the area.”

Grab an ice pack, get some rest and allow your injury to fully recover before trying to get stronger.

Strained and pulled muscle. “The first thing a person with a pulled or strained muscle should know is that they, like everyone, should warm up thoroughly before doing anything,” Greene notes.

She also says that people with this type of injury should stay in a pain-free range by focusing on conditioning the side of the body opposite of the strained or torn muscle. If you have pulled a hamstring, for example, then aim to work on your upper-body.

Greene also notes that there are preventative measures that a person can take to avoid pulling or training a muscle. First, Greene recommends a good warm-up for five to 10 minutes. Second, be sure to cool down at the end of your workout. And don’t forget to stretch.

“We find that as people age, they can actually pull muscles by doing everyday things such as bending over to grab a bag of groceries or leaning over to put something on a shelf,” she explains. “So the preventative measures that can be taken to avoid pulling or tearing a muscle with exercise are also measures that should be taken to avoid tearing or pulling a muscle in everyday life, not just on a basketball court.”

Overall, Greene believes the most important thing injured exercisers can do when hitting the gym is to pay attention to their body. She also advises to stop immediately if a workout becomes painful.  

“One of the basic exercise myths is ‘no pain, no gain.’ We used to think that a long time ago,” says Greene. “If you are actually in pain, you should stop immediately. Now we say, ‘no discomfort, no gain.’ There is a big difference.”

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Article adapted by MD Sports from original press release.
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MFit, the Health Promotion Division of the University of Michigan Health System (UMHS) provides medically-based personalized health and wellness programs and services to UMHS patients, UM employees, the greater Washtenaw County community, and employers in Michigan.

Source: Laura Drouillard
University of Michigan

Teenage girls use steroids too

Researchers from the Division of Health Promotion & Sports Medicine at Oregon Health & Science University have found steroid use among teen girls is not limited to athletes and often goes hand in hand with other unhealthy choices, including smoking and taking diet pills. The study was published in the Archives of Pediatrics & Adolescent Medicine, a JAMA/Archives journal.Diane Elliot, M.D., professor of medicine (health promotion and sports medicine), OHSU School of Medicine, and colleagues analyzed findings from the Center for Disease Control’s Youth Risk Behavior Survey of 7,544 ninth- through 12th-grade girls from around the country. The questionnaire asked about sports participation, anabolic steroid and drug use, and other illegal or unhealthy behaviors. Approximately 5 percent of participants reported prior or ongoing anabolic steroid use.

In addition to greater substance use, young female steroid users were more likely to have had sexual intercourse before age 13; have been pregnant; drink and drive or have ridden with a drinking driver; carry a weapon; have been in a fight on school property; have feelings of sadness or hopelessness almost every day for at least two weeks; and have attempted suicide. Those reporting anabolic steroid use were less likely to participate in team athletics.

Overall, more than two-thirds of those surveyed reported trying to change their weight. Girls who used steroids were more likely try extreme weight-loss techniques, such as vomiting and laxative use.

Adolescent girls reporting anabolic steroid use had significantly more other health-harming behaviors, Elliot explained, “They were much more likely to use other unhealthy substances, including cigarettes, alcohol, marijuana and cocaine.”

“Across all grades, these seem to be troubled adolescents with co-occurring health-compromising activities in the domains of substance use, sexual behavior, violence and mental health,” Elliot said. “Anabolic steroid use is a marker for high-risk girls. High-risk young women have received less attention than young men, perhaps reflecting that their actions are less socially, albeit more personally, destructive. Further study is needed to develop effective interventions for these young women.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: Tamara Hargens
Oregon Health & Science University

Use, misuse and abuse of drugs shakes foundations of amateur and professional sports?

Baseball team owners, players and fans seem to agree on the importance of drug testing for steroids, according to current reports, but the entire scope of performance-enhancing substances available for all athletes is vastly broader and many of the drugs employed by athletes are not easily detectable, says a Penn State researcher.”The use, misuse and abuse of drugs have long shaken the foundations of amateur and professional sports–baseball, football, track and field, gymnastics and cycling, to name just a few,” says Dr. Charles Yesalis, Penn State professor of exercise and sport science and health policy and administration. “The problem is not new. But like the rest of technology, doping in sport has grown in scientific and ethical complexity. In addition to drugs, we have natural hormones, blood doping, diuretics, nutritional supplements, social and recreational drugs, stimulants and miscellaneous substances, some of which may not even be on any list of banned substances.”

While drug testing technology struggles to keep up, an array of new and emerging technologies has arrived or is on the horizon with potential for abuse by athletes including gene transfer therapy, stem cell transplantation, muscle fiber phenotype transformation, red blood cell substitutes and new drug delivery systems, says Yesalis

“It is not too hard to imagine the day when muscles can be selectively enlarged or contoured,” according to the book. “Just imagine the consequences of a kinesiologist isolating specific muscles and selectively injecting designer genes into those muscles to maximize their function.”

The new book brings together the latest and most comprehensive scientific information about performance-enhancing substances, as well as discussion of drug testing, legal and social issues, and future directions by sports governing organizations.

“Sport has a responsibility to maintain a level playing field for the trial of skill,” Yesalis says. “The use of chemical and pharmacologist agents is cheating – just like using a corked baseball bat. But unlike the bat, doping is shrouded in mystery. Athletes and their advisors are constantly seeking ‘gray areas” surrounding the rules, and if something is not explicitly banned, then why not try it. This slippery slope of rationalization is treacherous and appealing to a player or team seeking glory and money rewards.”

In one chapter, “Drug Testing and Sport and Exercise,” author R. Craig Kammerer suggests that improvement in current tests and developments in new methods will assist future policymaking by athletic federations. However, effective testing must become more widespread and include unannounced testing outside of competition. Sanctions against athletes must be more fairly and uniformly applied, with thorough investigation to avoid false positive results and ruin an athlete’s career.

The difficulty of detecting and preventing the abuse of performance enhancing substances by adult athletes may seem futile but remains necessary as part of the effort to discourage abuse by youths who emulate professional athletes and also seek a winning advantage, Yesalis notes.

A recent government study of adolescent drug use shows an alarming increase in anabolic steroid use among middle school youths from 1998-1999 with an estimated 2.7 percent of eighth graders saying they have used the drugs. A larger survey by Blue Cross and Blue Shield estimates that one million U.S. children between the ages of 12 and 17 may have taken performance-enhancing substances including creatine, according to the book.

“Children and teens can seriously harm their future health by misusing these substances,” Yesalis says. “For example, steroids alone can cause scarring acne, hair loss and testicular atrophy, and may increase the risk of stroke and heart disease. It is just as important to note that little is known about the health consequences of many of the other substances used to enhance performance. Yet some coaches and parents look the other way and even actively encourage the use of performance-enhancing substances in pursuit of scholarships and winning.

“There is too much fame and fortune to be gained by being a winner in sports,” he notes. “It’s interesting to see that baseball fans being polled support drug testing and a ban on steroids, but it will take fans of all major sports to take a stand by turning off their TV sets or not buying a ticket to sports events before adult athletes, coaches and team owners stop trying to cheat. And, that’s probably not going to happen.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: Vicki Fong
Penn State

Individuals take 16 steps more to run a mile than walk

A new pair of studies compare step counts needed to meet 1) ACSM/CDC recommendations for moderate physical activity and 2) a one-mile mark. Both studies are useful as suggested step-based guidelines for meeting physical activity recommendations.

The first study, funded by the Centers for Disease Control and Prevention, was designed to translate ACSM/CDC public health guidelines for 30 minutes of daily moderate-intensity physical activity into steps. Researchers at San Diego State University and Arizona State University utilized commercial pedometers on a community sample of adults. Their results support an approximate 100 step/minute recommendation for minimally moderate intensity. To meet ACSM/CDC recommendations, this equates to 3,000 steps in 30 minutes, or three daily bouts of 1,000 steps in 10 minutes.

While pedometers are useful tools to measure step counts, this team notes pedometer-derived steps should be used with caution for gauging moderate intensity walking. Step counts associated with moderate intensity walking should be individualized based on stride length and level of fitness. ACSM defines moderate intensity walking as “brisk” walking, or “walking with purpose.” Walkers should be able to talk comfortably at a moderate-intensity level, but still feel exertion. Other definitions have included a pace at which you break a sweat and/or have a slight increase in your heart rate.

“Walking is one of the easiest forms of physical activity, and one that most people can do to meet recommendations for daily exercise,” said Simon J. Marshall, Ph.D., lead author of the study. “Most people have an instinct about the length of time or the distance they walk. A pedometer can help count steps, but when you also try to walk at least 1000 steps in 10 minutes on a regular basis, you may gain significant health benefits. For inactive people, setting smaller targets can help them start a program to meet general physical activity guidelines and enhance their health and wellness.”

In the one-mile study, researchers at Boise State University wanted to determine the number of steps individuals take while walking one mile at 20 and 15-minute paces and while running the same distance at 12, 10, eight, and six-minute paces. One mile (1,609 meters) step count varies at different walking and running speeds and can be predicted based on gender, pace, and height or leg length.

The average number of steps required to run/walk a mile ranged from 1,064 steps for a six-minute-mile pace in men to 2,310 steps for a 20-minute per mile walk in women. An interesting finding is that on average, individuals took more steps while running (jogging) a 12-minute mile than while walking a 15-minute mile (1,951 vs.1,935 steps, respectively). This finding is most likely related to the smaller distance between steps that people tend to take while jogging at the slower speed (12-minute mile) compared to walking at a 15-minute per mile pace.

“A ‘mile’ appears to be universally known as a marker of distance for walkers and runners to measure their activity achievements,” said Werner Hoeger, Ed.D., FACSM, lead author. “To estimate the number of steps required to walk or run a mile at selected speeds is likely to help people who monitor their steps with a pedometer with the objective of increasing their fitness by working up the miles.”

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Article adapted by MD Sports Weblog from original press release.
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The American College of Sports Medicine is the largest sports medicine and exercise science organization in the world. More than 20,000 international, national, and regional members are dedicated to advancing and integrating scientific research to provide educational and practical applications of exercise science and sports medicine.

http://www.acsm.org

Super protein creates fat burning Metabolic ’shield” against weight gain…

And it increases endurance to run a mile and decreases inflammation

The Salk Institute scientist who earlier discovered that enhancing the function of a single protein produced a mouse with an innate resistance to weight gain and the ability to run a mile without stopping has found new evidence that this protein and a related protein play central roles in the body’s complex journey to obesity and offer a new and specific metabolic approach to the treatment of obesity related disease such as Syndrome X (insulin resistance, hyperlipidemia and atherosclerosis).

Dr. Ronald M. Evans, a Howard Hughes Medical Investigator at The Salk Institute’s Gene Expression Laboratory, presented two new studies (date) at Experimental Biology 2005 in the scientific sessions of the American Society for Biochemistry and Molecular Biology. The studies focus on genes for two of the nuclear hormone receptors that control broad aspects of body physiology, including serving as molecular sensors for numerous fat soluble hormones, Vitamins A and D, and dietary lipids.

The first study focuses on the gene for PPARd, a master regulator that controls the ability of cells to burn fat. When the “delta switch” is turned on in adipose tissue, local metabolism is activated resulting in increased calorie burning. Increasing PPARd activity in muscle produces the “marathon mouse,” characterized by super-ability for long distance running. Marathon mice contain altered muscle composition, which doubles its physical endurance, enabling it to run an hour longer than a normal mouse. Marathon mice contain increased levels of slow twitch (type I) muscle fiber, which confers innate resistance to weight gain, even in the absence of exercise.

Additional work to be reported at Experimental Biology looks at another characteristic of PPARd: its role as a major regulator of inflammation. Coronary artery lesions or atherosclerosis are thought to be sites of inflammation. Dr. Evans found that activation of PPARd suppresses the inflammatory response in the artery, dramatically slowing down lesion progression. Combining the results of this new study with the original “marathon mouse” findings suggests that PPARd drugs could be effective in controlling atherosclerosis by limiting inflammation and at the same time promoting improved physical performance.

Dr. Evans says he is very excited about the therapeutic possibilities related to activation of the PPARd gene. He believes athletes, especially marathon runners, naturally change their muscle fibers in the same way as seen in the genetically engineered mice, increasing levels of fat-burning muscle fibers and thus building a type of metabolic ’shield” that keeps them from gaining weight even when they are not exercising.

But athletes do it through long periods of intensive training, an approach unavailable to patients whose weight or medical problems prevent them from exercise. Dr. Evans believes activating the PPARd pathway with drugs (one such experimental drug already is in development to treat people with lipid metabolism) or genetic engineering would help enhance muscle strength, combat obesity, and protect against diabetes in these patients.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Sarah Goodwin
Federation of American Societies for Experimental Biology

Growth-boosting hormone “Pumps up” plants like athletes on steroids

When given extra shots of the plant steroid brassinolide, plants “pump up” like major league baseball players do on steroids. Tracing brassinolide’s signal deep into the cell’s nucleus, researchers at the Salk Institute for Biological Studies have unraveled how the growth-boosting hormone accomplishes its job at the molecular level.The Salk researchers, led by Joanne Chory, a professor in the Plant Molecular and Cellular Biology Laboratory and a Howard Hughes Medical Institute investigator, published their findings in this week’s journal Nature.

“The steroid hormone brassinolide is central to plants’ growth. Without it, plants remain extreme dwarfs. If we are going to understand how plants grow, we need to understand the response pathway to this hormone,” says Chory. “This study clarifies what’s going on downstream in the nucleus when brassinolide signals a plant cell to grow.”

Brassinolide, a member of a family of plant hormones known as brassinosteroids, is a key element of plants’ response to light, enabling them to adjust growth to reach light or strengthen stems. Exploiting its potent growth-promoting properties could increase crop yields or enable growers to make plants more resistant to drought, pathogens, and cold weather.

Unfortunately, synthesizing brassinosteroids in the lab is complicated and expensive. But understanding how plant steroids work at the molecular level may one day lead to cheap and simple ways to bulk up crop harvests.

Likewise, since low brassinolide levels are associated with dwarfism, manipulating hormone levels during dormant seasons may allow growers to control the height of grasses, trees or other plants, thereby eliminating the need to constantly manicure gardens.

Based on earlier studies, the Salk researchers had developed a model that explained what happens inside a plant cell when brassinolide signals a plant cell to start growing.

But a model is just a model. Often evidence in favor of a particular model is indirect and could support multiple models. Describing the components of the signaling cascade that relays brassinolide’s message into a cell’s nucleus, postdoctoral researcher and lead author of the study Grégory Vert, now at the Centre national de la recherche scientifique (CNRS) in Montpellier, France, said, “All the players are old acquaintances and we knew from genetic studies that they were involved in this pathway. But when we revisited the old crew it became clear that we had to revise the original model.”

When brassinosteroids bind a receptor on the cell’s surface, an intracellular enzyme called BIN2 is inactivated by an unknown mechanism. Previously, investigators thought that inactivation of BIN2, which is a kinase, freed a second protein known as BES1 from entrapment in the cytoplasm, the watery compartment surrounding a cell’s nucleus, and allowed it to migrate or “shuttle” into the nucleus where it tweaked the activity of genes regulating plant growth.

A closer inspection, however, revealed that BIN2 resides in multiple compartments of a cell, including the nucleus, and it is there–not in the cytoplasm–that BIN2 meets up with BES1 and prevents it from activating growth genes. “All of a sudden the ‘BES1 shuttle model’ no longer made sense,” says Vert, adding that it took many carefully designed experiments to convince himself and others that it was time to retire the old model.

A new picture of how brassinosteroids stimulate plant growth now emerges based on those experiments: steroid hormones are still thought to inactivate BIN2 and reciprocally activate BES1, but instead of freeing BES1 to shuttle into the nucleus, it is now clear that the crucial activation step occurs in the nucleus where BES1 is already poised for action. Once released from BIN2 inhibition, BES1 associates with itself and other regulatory factors, and this modified form of BES1 binds to DNA, activating scores of target genes.

Referring to the work of Vert and other members of the brassinosteroid team, Chory says, “The old model may be out, but Greg’s new studies, together with those of former postdocs, Yanhai Yin and Zhiyong Wang, have allowed us to unravel the nuclear events controlling brassinosteroid responses at the genomic level. This turns our attention to the last mystery: the gap in our understanding of the events between steroid binding at the cell surface and these nuclear mechanisms.”

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

The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.

New muscle-building agent more effective than all previous ones

The Johns Hopkins scientists who first created “mighty mice” have developed, with pharmaceutical company Wyeth and the biotechnology firm MetaMorphix, an agent that’s more effective at increasing muscle mass in mice than a related potential treatment for muscular dystrophy now in clinical trials.

The new agent is a version of a cellular docking point for the muscle-limiting protein myostatin. In mice, just two weekly injections of the new agent triggered a 60 percent increase in muscle size, the researchers report in the Proceedings of the National Academy of Sciences, published and available publicly through the journal’s website.

The researchers’ original mighty mice, created by knocking out the gene that codes for myostatin, grew muscles twice as big as normal mice. An antibody against myostatin now in clinical trials caused mice to develop muscles 25 percent larger than those of untreated mice after five weeks or more of treatment.

The researchers’ expectation is that blocking myostatin might help maintain critical muscle strength in people whose muscles are wasting due to diseases like muscular dystrophy or side effects from cancer treatment or AIDS.

“This new inhibitor of myostatin, known as ACVR2B, is very potent and gives very dramatic effects in the mice,” says Se-Jin Lee, M.D., Ph.D., a professor of molecular biology and genetics in Johns Hopkins’ Institute for Basic Biomedical Sciences. “Its effects were larger and faster than we’ve seen with any other agent, and they were even larger than we expected.”

ACVR2B is the business end of a cellular docking point for the myostatin protein, and it probably works in part by mopping up myostatin so it can’t exert its muscle-inhibiting influence. But the researchers’ experiments also show that the new agent’s extra potency stems from its ability to block more than just myostatin, says Lee.

“We don’t know how many other muscle-limiting proteins there may be or which ones they are,” says Lee, “but these experiments clearly show that myostatin is not the whole story.”

The evidence for other players came from experiments with mighty mice themselves. Because these mice don’t have any myostatin, any effects of injecting the new agent would come from its effects on other proteins, explains Lee. After five injections over four weeks, mighty mice injected with the new agent had muscles 24 percent larger than their counterparts that didn’t get the new agent.

“In some ways this was supposed to be a control experiment,” says Lee. “We weren’t really expecting to see an effect, let alone an effect that sizeable.”

In other experiments with normal female mice, weekly injections of the new agent provided the biggest effect on muscle growth after just two weeks at the highest dose given (50 milligrams per kilogram mouse weight). Depending on the muscle group analyzed, the treated mice’s muscles were bigger than untreated mice by 39 percent (the gastrocnemius [calf] muscle) to 61 percent (the triceps).

After just one week, mice given a fifth of that highest dose had muscles 16 percent to 25 percent bigger than untreated mice, depending on the muscle group analyzed, and mice treated with one injection a week for two, three or four weeks continued to gain muscle mass.

But although the new agent seems quite promising, its advantage in potency also requires extra caution. “We don’t know what else the new agent is affecting or whether those effects will turn out to be entirely beneficial,” says Lee.

Lee says they also are conducting experiments with the mice now to see whether the effect lasts after injections cease and whether it helps a mouse model of muscular dystrophy retain enough muscle strength to prolong life.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Joanna Downer
Johns Hopkins Medical Institutions

The research was funded by grants from the National Institute of Child Health and Human Development and the National Cancer Institute and by funds from Wyeth Research and MetaMorphix Inc. The new agent was produced and first tested at Wyeth, and the inhibitor used in the current mouse studies was produced at MetaMorphix. All of the mouse studies described in this article and in the PNAS paper were conducted in Lee’s laboratory at Johns Hopkins.

Authors on the report are Se-Jin Lee and Suzanne Sebald of Johns Hopkins; Lori Reed of Wyeth Exploratory Drug Safety, and Monique Davies, Stefan Girgenrath, Mary Goad, Kathy Tomkinson, Jill Wright and Neil Wolfman of Wyeth Discovery Research; Christopher Barker, Gregory Ehrmantraut, James Holmstrom and Betty Trowell of MetaMorphix Canada; Barry Gertz, Man-Shiow Jiang, Li-fang Liang, Edwin Quattlebaum and Ronald Stotish of MetaMorphix, Beltsville, Md.; Martin Matzuk of Baylor College of Medicine; and En Li of Harvard Medical School.

Myostatin was licensed by The Johns Hopkins University to MetaMorphix and sublicensed to Wyeth. Lee is entitled to a share of sales royalty received by The Johns Hopkins University from sales of this factor. The Johns Hopkins University and Lee also own MetaMorphix stock, which is subject to certain restrictions under university policy. Lee is a paid consultant to MetaMorphix. The terms of these arrangements are being managed by the university in accordance with its conflict of interest policies.

On the Web: http://www.pnas.org/cgi/content/abstract/0505996102v1

Small doses of daily meditation improve focus and performance

Researchers at the University of Pennsylvania say that practicing even small doses of daily meditation may improve focus and performance.

Meditation, according to Penn neuroscientist Amishi Jha and Michael Baime, director of Penn’s Stress Management Program, is an active and effortful process that literally changes the way the brain works. Their study is the first to examine how meditation may modify the three subcomponents of attention, including the ability to prioritize and manage tasks and goals, the ability to voluntarily focus on specific information and the ability to stay alert to the environment.

In the Penn study, subjects were split into two categories. Those new to meditation, or “mindfulness training,” took part in an eight-week course that included up to 30 minutes of daily meditation. The second group was more experienced with meditation and attended an intensive full-time, one-month retreat.

Researchers found that even for those new to the practice, meditation enhanced performance and the ability to focus attention. Performance-based measures of cognitive function demonstrated improvements in a matter of weeks. The study, published in the journal Cognitive, Affective, & Behavioral Neuroscience, suggests a new, non-medical means for improving focus and cognitive ability among disparate populations and has implications for workplace performance and learning.

Participants performed tasks at a computer that measured response speeds and accuracy. At the outset, retreat participants who were experienced in meditation demonstrated better executive functioning skills, the cognitive ability to voluntarily focus, manage tasks and prioritize goals. Upon completion of the eight-week training, participants new to meditation had greater improvement in their ability to quickly and accurately move and focus attention, a process known as “orienting.” After the one-month intensive retreat, participants also improved their ability to keep attention “at the ready.”

The results suggest that meditation, even as little as 30 minutes daily, may improve attention and focus for those with heavy demands on their time. While practicing meditation may itself may not be relaxing or restful, the attention-performance improvements that come with practice may paradoxically allow us to be more relaxed.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Jordan Reese
University of Pennsylvania

The research was supported by the National Institutes of Health and the Penn Stress Management Program.

Scientists encourage genetic research into athletic ability to benefit sport and public health

Genetic research into athletic ability should be encouraged for its potential benefits in both sport and public health, a leading group of scientists meeting at the University of Bath said today. Genetic research into athletic ability should be encouraged for its potential benefits in both sport and public health, a leading group of scientists meeting at the University of Bath said today.

However, ethical concerns, such as whether seeking information about differences between ethnic groups could be perceived as racist research, need to be properly addressed, they warn.

Their recommendations are published in a ‘position stand’ on genetic research and testing launched at the British Association of Sport & Exercise Sciences annual meeting today.

They call for more genetic research in the sport and exercise sciences because of the anticipated benefits for public health, but want researchers to take a more active role in debating the implications of their work with the public.

“If a powerful muscle growth gene was identified, on the one hand this could help develop training programmes that increase muscle size and strength in athletes, but even more importantly the knowledge could be used to develop exercise programmes or drugs to combat muscle wasting in old age,” said Dr Alun Williams from Manchester Metropolitan University, one of the report’s authors.

“We, as scientists investigating genetics, acknowledge a public concern about some genetic research and we believe scientists need to engage in public in debates about the potential benefits of their research.

“Research into the athletic success of East African distance runners or sprinters of West African ancestry might be perceived as unethical.

“But understanding the limits of human exercise capacity in sport could lead to the development of treatments for a range of diseases like cancer and cardiovascular disease.”

The potential applications of genetic testing in sport and exercise also raise some ethical concerns, for example in identifying potential athletic ability before birth.

An Australian company already offers the first genetic performance test (for the ACTN3 gene) which has been linked to sprint and power performance.

The report authors are sceptical about whether this test is useful but anticipate that more advanced versions of these tests will be available in future.

“We are not yet at a point where we can identify a potential future Olympic champion from genetic tests but we may not be very far away,” said Dr Williams, who wrote the report with Drs Henning Wackerhage (Aberdeen University), Andy Miah (University of Paisley), Roger Harris (University of Chichester) and Hugh Montgomery (University College London).

They highlight two dangers of genetic performance tests. Firstly, genetic performance tests might later be linked to disease. For example, a muscle growth gene may later be linked to cancer growth.

“Not all people may want to know, while young that they are at increased risk of cancer by early middle age, but they might inadvertently become aware of that just because they had a ‘sport gene’ test,” said Dr Williams.

Secondly, genetic performance tests can be performed even before birth and this may lead to the selection of foetuses or to abortions based on athletic potential.

The report recommends genetic counselling and that the testing should be confined to mature individuals who fully understand the relevant issues.

Genetic tests might also be used to screen for health risks during sport such as genes that are linked to sudden cardiac death.

Genetic tests for sudden cardiac death are already available but the report recommends that such testing should not be enforced on athletes.

Problems with mandatory testing are highlighted by the case of the basketball player Eddy Curry, who had an irregular heart beat.

Curry was asked by his club, the Chicago Bulls, to perform a predictive genetic test for a heart condition. The athlete refused and was traded to the New York Knicks who did not make such a demand.

In future, genetic tests might be used to identify those that respond with the biggest drop in cholesterol, blood pressure or glucose to exercise.

In a personalised medicine approach, such tests could be used to select subjects for therapeutic exercise programmes but scientists are concerned that this might undermine the ‘exercise for all’ message that already seems difficult to get across to the public.

The authors say that genetic testing might also be used to detect gene doping, which may be a real threat by the time of the London Olympics in 2012, or to show that positive doping tests are the result of a genetic mutation in an athlete.

The report recommends that genetic testing should be used for anti-doping testing as long as the genetic samples are destroyed after testing.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Andrew McLaughlin
University of Bath