Skeletal Muscle Research - The Most Abundant Tissue in the Human Body

Skeletal muscle is the most abundant of the human body's tissues. It consists of thread-like cells - the longest can be up to 30 cm long and 0.15 mm thick - that are bound together into strands by collagen filaments. In turn, these strands weave themselves into cords, bundles and sheets of pliable tissue.

A single muscle cell (called a fibre) is made up of an external membrane; many scattered nuclei, which lie along the fibre's length just under the membrane; and thousands of inner strands, called myofibrils, which constitute the bulk of the cell's contents.

These myofibrils are the same length as the parent cell and cause it to contract forcefully in response to nerve impulses. In leg muscles, a single motor neuron may control several hundred to 1000 or more muscle fibres. However, for the extreme motor precision of gripping a dime or seeing a distant object, the ratio of neuron to fibre can be almost one-to-one.

To Exercise or Not to Exercise

Vigorous training with weights can double or triple a muscle's size. Muscles respond to exercise in two ways. First off, a cascade of biomechanical and biochemical signals prompt local satellite cells scattered throughout the warp and woof of muscle tissue to divide in two. Then the nuclei of these satellite daughter cells fuse with adjacent fibres, adding bulk and mass to muscle. Muscle fibres can also accelerate their rate of protein synthesis so that muscle tissue bulks up without the necessity of adding more nuclei.

Inactivity has the opposite effect. Disuse, as when someone is confined to bed, can cause muscle fibres to shrink by as much as 20 per cent in only two weeks. And with aging come other changes to skeletal muscle. Most marked is the loss of muscle fibres, a condition called sarcopenia. Once most adults pass their physical prime, they lose an average of 10 ounces of lean body mass a year, mostly in the form of muscle tissue. It's an insidious process just like osteoporosis, and one few people notice until they find it's getting difficult to climb stairs or heft themselves off the sofa. Also, as we age, some motor neurons die. The nerve's muscle fibres are then left without any input, so they, too, atrophy and die - unless they are reinnervated by another motor neuron.

On the bright side, studies show it's never too late to regain some muscle strength. Regular weight lifting (one to five kilos) can stave off the loss of muscle mass as a whole by greatly thickening individual fibres, but it doesn't appear to reverse age-related loss of fibres and motor neurons.

From Muscular Dystrophy to Polymyositis

In addition to strains, sprains and outright trauma, there are many different diseases that affect skeletal muscle, including chronic pain syndromes, inflammatory arthritis, various types of paralysis and diseases that cause muscles to weaken and waste away.

Among the most difficult conditions to treat are muscular dystrophies. These genetic disorders are characterized by progressive muscle wasting that begins with microscopic changes in the muscle tissue. As a result of a genetic mutation on the X chromosome, dystrophies affect young or adolescent boys. Duchenne muscular dystrophy (DMD), one of the most common forms, inhibits muscle nuclei from producing an essential protein, called dystrophin. In its most severe form, DMD inexorably weakens the muscles of the arms, legs and torso, and affects the heart and the muscles that control breathing. Patients often die in early adulthood.

Polymyositis (PM) and dermatomyositis (DM) are two forms of inflammatory disease that cause profound muscle weakness - the main difference between the two is that DM can also cause a skin rash. Both conditions are thought to be autoimmune disorders, wherein the body's immune system attacks skeletal muscle. It's estimated that PM and DM combined affect about 20,000 people in North America, with approximately 1400 new adult cases per year. PM and DM affect blacks two to three times more often than whites, and they're twice as common among women as men. The disorders may appear at any time, but begin most commonly between ages 40 and 60.

Myasthenia gravis (MG) is a neuromuscular disease that causes weakness and fatigue, most commonly in the muscles of the eyes, face, throat and limbs. MG occurs when immune-system antibodies attack the muscles' acetylcholine receptors, which normally receive messages from nerve cells. When this nerve-muscle communication is disrupted, the muscle can't contract as forcefully as it usually does, and the result is muscle weakness. Women most often develop MG in their late teens and twenties, while for men onset is usually after age 60. Population-health data suggest that MG currently affects about 25,000 people in North America.

New Technologies, New Treatments

Canadian researchers are internationally recognized experts in the genetics, biochemistry and developmental biology of muscle tissue. For example, Canada's muscle stem-cell research holds great promise for muscle-replacement treatment and gene therapies for muscular dystrophies.

IMHA is currently working to unite the muscle-research community and integrate its efforts to better understand the basic science of muscle tissue from the biology of cell architecture, stem-cell activation and how neurons nourish muscle fibres to muscle tissue's response (at the genetic and molecular levels) to exercise or inactivity, how to forestall or reverse sarcopenia and how age and disease changes muscle's microvasculature.

And with new technologies such as micro arrays and proteomics yielding new insights into muscle gene expression and protein functions, the whole spectrum of Canadian muscle research - from basic science and epidemiology to clinical and musculoskeletal (MSK) rehabilitation sciences - is about to change in ways that we could have never imagined even a decade ago.

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