Muscle atrophy

Muscle atrophy is defined as a decrease in the mass of the muscle; it can be a partial or complete wasting away of muscle. When a muscle atrophies, it becomes weaker, since the ability to exert force is related to mass; muscle atrophy is a co-morbidity of several common diseases, including cancer, AIDS, congestive heart disease, COPD (chronic obstructive pulmonary disease), renal failure, and severe burns; patients who have "cachexia" in these disease settings have a poor prognosis.

Clinical settings of atrophy

There are many diseases and conditions which cause a decrease in muscle mass, known as atrophy, including: Dejerine Sottas syndrome (HSMN Type III), inactivity, as seen when a cast is put on a limb, or upon extended bedrest (which can occur during a prolonged illness); cachexia - which is a "body-wasting" syndrome that is a co-morbidity of cancer and Congestive Heart Failure; Chronic Obstructive Pulmonary Disease; burns, liver failure, etc. Other syndromes or conditions which can induce skeletal muscle atrophy are congestive heart disease, liver disease, and starvation.

Quality of life

Muscular atrophy decreases quality of life as the sufferer becomes unable to perform certain tasks or worsen the risks of accidents while performing those (like walking). Muscular atrophy affects a major number of elderly.

Other muscles diseases, distinct from atrophy

During aging, there is a gradual decrease in the ability to maintain skeletal muscle function and mass. This condition is called "sarcopenia". The exact cause of sarcopenia is unknown, but it may be due to a combination of the gradual failure in the "satellite cells" which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors which are necessary to maintain muscle mass and satellite cell survival.

In addition to the simple loss of muscle mass (atrophy), or the age-related decrease in muscle function (sarcopenia), there are other diseases which may be caused by structural defects in the muscle (muscular dystrophy), or by inflammatory reactions in the body directed against muscle (the myopathies).

Pathophysiology

Muscle atrophy occurs by a change in the normal balance between protein synthesis and protein degradation. During atrophy, there is a down-regulation of protein synthesis pathways, and an activation of protein breakdown pathways. The particular protein degradation pathway which seems to be responsible for much of the muscle loss seen in a muscle undergoing atrophy is the "ATP-dependent, ubiquitin/proteasome pathway. In this system, particular proteins are targeted for destruction by the ligation of at least four copies of a small peptide called ubiquitin onto a substrate protein. When a substrate is thus "poly-ubiquitinated", it is targeted for destruction by the proteasome. Particular enzymes in the ubiquitin/proteasome pathway allow ubiquitination to be directed to some proteins but not others - specificity is gained by coupling targeted proteins to an "E3 ubiquitin ligase". Each E3 ubiquitin ligase binds to a particular set of substrates, causing their ubiquitination.

Potential treatment

Muscle atrophy can be opposed by the signaling pathways which induce muscle hypertrophy, or an increase in muscle size. Therefore one way in which exercise induces an increase in muscle mass is to downregulate the pathways which have the opposite effect.

One important rehabilitation tool for muscle antrophy includes the use of functional electrical stimulation to stimulate the muscles. This has seen a large amount of success in the rehabilitation of paraplegic patients.