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, this leads to muscle weakness,
since the ability to exert force is related to mass. Muscle atrophy results from a co-morbidity
of several common diseases, including cancer, AIDS, congestive heart failure, COPD, renal
failure, and severe burns; patients who have "cachexia" in these disease settings have
a poor prognosis. Moreover, starvation eventually leads to muscle atrophy. Disuse of the muscles
will also lead to disuse atrophy while neurogenic atrophy is muscle atrophy that results from
damage to the nerve that stimulates the muscle. Also, time in a circa zero g environment without
exercise will lead to atrophy. This is partially due to the smaller amount of exertion needed
to move about, and that muscles are not used to maintain posture.
Clinical settings There are many diseases and conditions which
cause a decrease in muscle mass, known as atrophy, including: Dejerine Sottas syndrome,
inactivity, as seen when a cast is put on a limb, or upon extended bedrest; cachexia
- which is a 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 liver disease, and starvation.
Quality of life Muscular atrophy decreases qualities of life
as the sufferer becomes unable to perform certain tasks or worsen the risks of accidents
while performing those. Muscular atrophy increases the risks of falling in conditions such as
IBM. Muscular atrophy affects a major number of elderly.
Other muscle 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, or the age-related decrease in muscle function,
there are other diseases which may be caused by structural defects in the muscle, or by
inflammatory reactions in the body directed against muscle.
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
protein degradation. 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 atrophy 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. Since the absence of muscle-building amino
acids can contribute to muscle wasting, amino acid therapy may be helpful for regenerating
damaged or atrophied muscle tissue. The branched-chain amino acids or BCAAs are critical to this
process, in addition to lysine and other amino acids.
In severe cases of muscular atrophy, the use of an anabolic steroid such as methandrostenolone
is administered to patients as a potential cure. A novel class of drugs, called SARM
are being investigated with promising results. They would have fewer side-effects, while
still promoting muscle and bone tissue growth and regeneration. These claims are, however,
yet to be confirmed in larger clinical trials. Quantification
A CT scan can distinguish muscle tissue from other tissues and thereby estimate the amount
of muscle tissue in the body. Fast loss of muscle tissue, can be approximated
by the amount of urea in the urine. The equivalent nitrogen content of urea can be estimated
by the conversion factor 0.028 g/mmol. Furthermore, 1 gram of nitrogen is roughly equivalent to
6 gram of protein, and 1 gram of protein is roughly equivalent to 4 gram of muscle tissue.
Subsequently, in situations such as muscle wasting, 1 mmol of excessive urea in the
urine roughly corresponds to a muscle loss of 0.67 gram.
Hibernation Inactivity and starvation in mammals lead
to atrophy of skeletal muscle, accompanied by a smaller number and size of the muscle
cells as well as lower protein content. In humans, prolonged periods of immobilization,
as in the cases of bed rest or astronauts flying in space, are known to result in muscle
weakening and atrophy. Such consequences are also noted in small hibernating mammals like
the golden-mantled ground squirrels and brown bats.
Bears are an exception to this rule; species in the family Ursidae are famous for their
ability to survive unfavorable environmental conditions of low temperatures and limited
nutrition availability during winter by means of hibernation. During that time, bears go
through a series of physiological, morphological and behavioral changes. Their ability to maintain
skeletal muscle number and size at time of disuse is of significant importance.
During hibernation, bears spend four to seven months of inactivity and anorexia without
undergoing muscle atrophy and protein loss. There are a few known factors that contribute
to the sustaining of muscle tissue. During the summer period, bears take advantage of
the nutrition availability and accumulate muscle protein. The protein balance at time
of dormancy is also maintained by lower levels of protein breakdown during the winter time.
At times of immobility, muscle wasting in bears is also suppressed by a proteolytic
inhibitor that is released in circulation. Another factor that contributes to the sustaining
of muscle strength in hibernating bears is the occurrence of periodic voluntary contractions
and involuntary contractions from shivering during torpor. The three to four daily episodes
of muscle activity are responsible for the maintenance of muscle strength and responsiveness
in bears during hibernation. See also
Brown atrophy of the heart Effect of spaceflight on the human body
Muscle weakness Muscular dystrophy
Myotonic dystrophy Sarcopenia
Journal of Cachexia, Sarcopenia and Muscle References
External links Muscular atrophy at the US National Library
of Medicine Medical Subject Headings