New research points to possible treatments for muscle wasting disorders offers exciting news because FHL1 appears to modulate muscle mass and strength enhancement. The protein partners with and activates the transcription factor, NFATc1. Encouraging this partnership might provide a possible treatment for muscle wasting disorders. The article will appear in the December 15, 2008 issue of The Journal of Cell Biology (JCB).

Mutations in FHL1 are present in several myopathies, including reducing-body myopathy (RBM), but until now, both the molecular mechanisms causing the disease, and the regular function of FHL1 in healthy tissue, remained unknown.

To address this, Cowling et al. overexpressed FHL1 in both transgenic mice and cultured myoblasts. The mice developed skeletal muscle hypertrophy, and showed increased strength and endurance. Overexpression in myoblasts also increased cell fusion, resulting in hypertrophic myotubes. These phenotypes are similar to those caused by the calcineurin/NFAT pathway and, indeed, inhibiting calcineurin blocked the effects of FHL1 overexpression in vitro. The authors showed that FHL1 binds to and enhances the transcriptional activity of NFATc1 in vitro and in vivo.

So what goes wrong when FHL1 is mutated? In RBM, mutant FHL1 accumulates in cytoplasmic aggregates called reducing bodies, probably as a result of misfolding. When these mutants were expressed in cultured myoblasts, they also aggregated, and did not induce hypertrophy. Cowling and colleagues found that NFATc1 was sequestered to the aggregates, and was therefore unable to activate its target genes.

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Article adapted by Sandco from original press release.
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Contact: Rita Sullivan
Rockefeller University Press

Cowling, B.S., J Cell Biol. 2008 Dec 15;183(6):1033-48

Experts at The University of Nottingham are to investigate the effect of nutrients on muscle maintenance in the hope of determining better ways of keeping up our strength as we get old.

The researchers, based at the School of Graduate Entry Medicine and Health in Derby, want to know what sort of exercise we can take and what food we should eat to slow down the natural loss of skeletal muscle with ageing.

The team from the Department of Clinical Physiology, which has over 20 years experience in carrying out this type of metabolic study, need to recruit 16 healthy male volunteers in two specific age groups to help in it’s research.

Skeletal muscles make up about half of our body weight and are responsible for controlling movement and maintaining posture. However, at around 50 years of age our muscles begin to waste at approximately 0.5 per cent to one per cent a year. It means that an 80 year old may only have 70 per cent of the muscle of a 50 year old.

Since the strength of skeletal muscle is proportional to muscle size, such wasting makes it harder to carry out daily activities requiring strength, such as climbing stairs and leads to a loss of independence and an increased risk of falls and fractures.

In order for skeletal muscles to maintain their size, the large reservoirs of muscle protein require constant replenishment in the way of amino acids from protein contained within the food we eat. In fact, amino acids from our food act not only as the building blocks of muscle proteins but also actually ‘tell’ our muscle cells to build proteins.

Recent research from the clinical physiology team has shown that the cause of muscle wasting with ageing appears to be an attenuation of muscle building in response to protein feeding. In other words, as we age we lose the ability to covert the protein in the food we eat in to muscle tissue. The proposed research will investigate the mechanisms responsible for this deficit.

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Article adapted by MD Sports from original press release.
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Contact: Lindsay Brooke
University of Nottingham

Inhibiting a growth factor that keeps muscles from getting too big may optimize recovery of injured soldiers, researchers say. They are studying two myostatin inhibitors in mice with limb injuries, first to see which works best and then to identify the best delivery mechanism, says Dr. Mark Hamrick, one biologist in the Medical College of Georgia Schools of Graduate Studies and Medicine.

“Fifty to 60 percent of the injuries occurring in Iraq are to the limbs, and the average injury requires five surgeries,” Dr. Hamrick says. “Myostatin inhibitors are known to improve muscle regeneration and we have evidence that they also increase bone formation. We believe these inhibitors will result in a stronger, more rapid recovery for these soldiers and other victims of traumatic limb injuries.”

A $1.2 million grant from the Office of Naval Research to Dr. Hamrick is enabling laboratory studies of two experimental myostatin inhibitors: a decoy receptor and a binding protein, both developed by MetaMorphix, Inc. of Beltsville, Md. Both inhibitors have been shown effective in muscle regeneration, but this is the first trial that looks at their impact on bone.

Two delivery mechanisms also will be studied. “Is the best approach a single injection bolus that circulates everywhere or just localized delivery?” Dr. Hamrick says.

Study collaborators include Dr. Li Liang of the life sciences company MetaMorphix, who will oversee development of the inhibitors; Dr. Xuejun Wen, bioengineer at Clemson University in Clemson, S.C.; and David Immel, radiographic imaging expert at Savannah River National Laboratory in Aiken, S.C., who will provide three-dimensional, high-resolution computerized tomography scans of injured limbs before and after treatment.

Myostatin is primarily produced by muscle cells. Females tend to produce more myostatin receptors, which helps explain why men tend to have greater muscle mass. Dr. Hamrick’s lab also has found the receptor on bone-derived stem cells – needed to help repair an injury – and others have found it in healing fractures. “When you take it away, the healed callus that forms at the fracture site has more bone in it,” says Dr. Hamrick. “Myostatin also increases fibrosis and scarring within tissue so part of what you are doing is blocking that.”

Bone and muscle healing typically go hand in hand. Muscle provides blood, growth factors and potentially stem cells for a healing callus. It’s not yet known how well bones reciprocate. “If you can improve muscle healing, you can improve bone healing,” Dr. Hamrick says. “Young people have a tremendous potential to heal that can be improved with better approaches to preventing infection and to healing soft tissue and bone in an integrated manner.”

Researchers hope to move to clinical trials in two to three years, Dr. Hamrick says. “If we find the primary role of myostatin is very early in the healing process and see a big jump in expression early in a fracture callus, it may be that a single injection bolus immediately after injury is the best time for treatment rather than continued treatment over a period of time.”

Myostatin is most highly expressed during development, but adults have some as well, so blocking it still facilitates muscle growth and development, primarily in response to exercise. Myostatin expression also tends to rise following an injury, apparently to control proliferation of new and regenerating cells, Dr. Hamrick says. Although there is no FDA-approved myostatin inhibitor, body builders often take supplements that claim to reduce myostatin function and help build muscle.

A whole spectrum of naturally occurring genetic variations likely result in minor alterations in myostatin signaling that could help explain why some people are more muscular than others, Dr. Hamrick notes. In a separate study funded by the National Institutes of Health, he is using a genetically engineered ‘mighty mouse,’ which is missing the myostatin gene, to find the best way to optimize bone growth and help young people avoid osteoporosis. German researchers reported in 2004 in the New England Journal of Medicine the case of a child whose muscles already were bulging as a newborn apparently because of a dysfunctional myostatin gene.

Source: Medical College of Georgia

If you decide to make the choice to begin bodybuilding, it is good to keep in mind not to become too overzealous and burn itself out too quickly, or even worse, injure yourself. Someone beginning bodybuilding should take it as a gradual process that will eventually lead to more experienced exercise routines.

Below are some suggestions and tip’s for bodybuilding beginners if that is what you choose to pursue.

Diet And Bodybuilding

One of the most important aspects for beginning bodybuilders is diet. If you keep eating fast food or other kinds of junk food you cannot have any expectations to be successful at this sport. When it comes to sculpting your body discipline is one of the main necessities. That is why it is recommended by trainers that you start to consume primarily meat, nuts, fish, grain and milk. Foods such as these are low in fat, as well as high in protein that will assist in helping build muscle as well as increase your metabolism.

Your Workout Routine

Concerning your workout regimen, starting off slowly is important for beginners in this sport. Beginners in this activity in the beginning come to the realization that even though they really want to look as if they have the same physique as bodybuilders on the cover of magazines, or on TV, it is a work in progress. Bodybuilding beginners should start with two sets of repetitions with roughly a minute of rest in between.

They should do this for roughly 45 minutes, 4 days a week. After four weeks have passed, after allowing a body and a time to build itself up, at that point the bodybuilder can start to move gradually up to 60 minutes of a workout while doing three sets of repetitions with roughly a minute of rest in between. At approximately this point, their body should slowly start to change, muscle should be gained and fat should be lost.

Along with exercise and diet, rest is equally important with bodybuilding beginners. This is vitally important, as the individuals muscles need to grow during this period. At a minimum six to eight hours of sleep is recommended per night.

Whatever Your Desires and Goals Are

Whether you want to get into bodybuilding for competitive reasons or for your own personal achievement, it is essential for beginners in this sport to be on a gradual process. Making sure that proper rest, diet and exercise are accomplished is important to physical success. At first do not concern yourself about looking like a bodybuilder immediately; focus on a workout plan that will work for your specific body type as well as your specific goals.

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Author Resource:- Listen to Corbin Newlyn as he shares his insights as an expert author and an avid writer in the field of bodybuilding. If you would like to learn more go to Bodybuilding Advice and at Female Bodybuilding tips.

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