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(Anatomy) Muscles: Mighty Mouse, New Muscle-Building Agents

 
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adedios
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PostPosted: Tue Dec 13, 2005 7:52 am    Post subject: (Anatomy) Muscles: Mighty Mouse, New Muscle-Building Agents Reply with quote






Mouse Study: New Muscle-Building Agent Beats All Previous Ones
Johns Hopkins Medicine
Office of Corporate Communications
Media Contact: Joanna Downer
410-614-5105; jdowner1@jhmi.edu
December 8, 2005

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 online Dec. 5 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.

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.


--JHMI--

On the Web:
http://www.pnas.org/cgi/conten.....05996102v1

************************************************************

Questions to explore further this topic:

What are muscles?

http://www.nlm.nih.gov/medline.....0_no_0.htm
http://www4.tpgi.com.au/users/.....cular.html
http://kidshealth.org/kid/body/muscles_noSW.html
http://www.medphysics.wisc.edu/~jrc/muscles.htm

How does one grow and develop muscles?

http://kidshealth.org/kid/grow.....scles.html

What do muscles do?

http://yucky.kids.discovery.co.....00123.html
http://www.bbc.co.uk/health/kids/muscles.shtml

What is exercise?

http://kidshealth.org/kid/stay.....t_out.html

Muscles, workout, stretching:

http://www.sciencenewsforkids......ature1.asp

What is muscular dystrophy?

http://rarediseases.about.com/.....a/md05.htm

What is myostatin?

http://www.kidsnewsroom.org/ne.....ge=Science

GAMES

http://www.caerphilly.org.uk/P.....uscles.htm
http://www.nutritionexploratio.....s-main.asp
http://www.e-gfl.org/e-gfl/act.....cience.htm
http://vilenski.org/science/hu.....index.html


Last edited by adedios on Sat Jan 27, 2007 4:33 pm; edited 2 times in total
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adedios
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PostPosted: Fri Aug 11, 2006 7:21 am    Post subject: PRESSURE TO BE MORE MUSCULAR MAY LEAD MEN TO UNHEALTHY BEHAV Reply with quote

PRESSURE TO BE MORE MUSCULAR MAY LEAD MEN TO UNHEALTHY BEHAVIORS

10 August 2006
Ohio State University

COLUMBUS , Ohio – Women are not the only ones in American society who feel pressure to achieve the perfect body.

New research suggests that men feel pressure to have muscular bodies, and that influence can lead some to symptoms of eating disorders, pressure to use steroids, and an unhealthy preoccupation with weightlifting.

“Men see these idealized, muscular men in the media and feel their own bodies don't measure up,” said Tracy Tylka, author of the study and assistant professor of psychology at Ohio State University 's Marion campus.

“For some men, this can lead to unhealthy and potentially dangerous behaviors to try to reach that ideal.”

Tylka presented her research at a symposium August 10 in New Orleans at the annual meeting of the American Psychological Association.

Of course, women have been pressured for decades to achieve a thin ideal, but this is a more recent phenomenon for men, Tylka said.

“Instead of seeing a decrease in objectification of women in society, there has just been an increase in the objectification of men. And you can see that in the media today,” she said.

To test how this emphasis on muscularity has affected men, Tylka studied 285 college men. She asked them a variety of questions to determine how much pressure to be muscular that they felt from family, friends, romantic partners and the media.

The findings showed that the more pressure the men felt, the more they felt they had to live up to the ideals.


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“Men see these idealized, muscular men in the media and feel their own bodies don't measure up. For some men, this can lead to unhealthy and potentially dangerous behaviors to try to reach that ideal.”
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“They start to believe that the only attractive male body is a muscular one. And when they internalize that belief, they judge themselves on that ideal and probably come up short, because it is not a realistic portrayal of men,” she said.

While other studies have suggested men can become preoccupied with their muscles, Tylka said this research shows men are also very worried about their body fat.

“Not only are men being targeted to be muscular, but they also feel they have to be very lean to show off their muscularity.”

And the more dissatisfied that men in the study felt with their muscularity and body fat, the more they engaged in unhealthy behaviors, findings showed.

For example, men who were not happy with their muscles were more likely to say that their weight-training schedule interfered with other parts of their life, that others think they work out too much, that they used protein supplements, and even that they thought about using steroids.

Men who were dissatisfied with their body fat were more likely to report symptoms of eating disorders, such as avoiding certain foods, being terrified about being overweight, and being preoccupied with a desire to be thinner.

Tylka said there is a difference between men who exercise and watch their diet for their health, and those who do so because they feel pressure to change their bodies.

“It is good to exercise, to lift weights, and to eat the foods that make your body function well,” she said.

“But it is not good to be preoccupied with gaining muscle mass. Those that are preoccupied are not working out to get healthier, they are working out to bulk up. They are not eating healthy, they are cutting out major food groups like carbohydrates and eating massive amounts of protein.”

While men in American society are feeling increasing pressures to achieve the perfect body, Tylka said women still get a disproportionate share of the pressure.

“Women still get objectified more than men, but men are feeling the pressure too.”
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PostPosted: Fri Jun 15, 2007 1:00 pm    Post subject: Muscle weakness: New mutation identified Reply with quote

Blackwell Publishing Ltd.
14 June 2007

Muscle weakness: New mutation identified

New research, published in The Journal of Physiology, has identified a novel mutation associated with muscle weakness and distal limb deformities. The study demonstrates that muscle weakness experienced by persons with a regulatory protein tropomyosin mutation is directly related to a mechanism by which the mutant tropomyosin modulates contractile speed and force-generation capacity.

Dr. Julien Ochala and co-workers at the Department of Clinical Neurophysiology, University of Uppsala, in collaboration with scientists at the Department of Pathology, University of Göteborg, explored the mechanisms underlying the muscle weakness experienced by a woman and her daughter with a β-tropomyosin mutation, i.e., muscle weakness in the absence of macro or microscopic signs of muscle wasting. The results from single fibre contractile measurements and in vitro motility analyses demonstrated a mechanism where tropomyosin modulates myosin-actin kinetics. A slower motor protein myosin attachment rate to and a faster detachment rate from actin, caused by the mutation, results in a reduced number of myosin molecules in the strong actin binding state and muscle weakness. The results also implicate a potential role of the regulatory protein tropomyosin in modulating contractile speed and force-generation under physiological conditions.

It is suggested that the findings at the gene, protein and muscle cell levels in this specific neuromuscular disorder will have a significant impact on our understanding of the disease pathogenesis and provide important information for future therapeutic strategies. Walter R. Frontera, an independent expert, says: "Dr. Ochala and collaborators have published elegant proof of the clinical consequences of mutations in the regulatory proteins of skeletal muscles. Their data provide strong support for the dissociation between qualitative alterations in muscle contractility and quantitative evidence of muscle atrophy".
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