Muscle atrophy
There are many diseases and conditions which cause a decrease in
muscle mass, known as
atrophy. For example diseases such as cancer and
AIDS induce a body wasting syndrome called "
cachexia", which is notable for the severe muscle atrophy seen. Other syndromes or conditions which can induce skeletal muscle atrophy are congestive heart disease and liver disease. Also simple inactivity, as when a limb is put in a cast, or when a patient undergoes prolonged bed-rest, can induce significant loss of muscle tissue.
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).
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.
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.
