Automated Methods for the Analysis of Skeletal Muscle Fiber Size and Metabolic Type - International Review of Cell and Molecular Biology - page 275

the floor leading to atrophy of the hind-limb muscles similar to what occurs
in spaceflight ( Allen et al., 2009 ). Experiments utilizing this methodology
suggest that taurine ( Pierno et al., 2011 ) or electrical stimulation regimes
( Guo et al., 2012 ) can counteract the effect.
2.4. Denervation
Muscle fibers are stimulated to contract by motor neurons. With aging,
motor neurons are lost, which leads to denervation and atrophy of muscle
fibers and reductions of muscle mass ( Rowan et al., 2012 ). Denervation
accelerates after the age of 60 years and is a major contributing factor to
the loss of muscle strength among the elderly ( Deschenes, 2004 ). Denerva-
tion associated with aging is hypothesized to occur due to susceptibility of
the neurons to reactive oxygen species produced via aerobic metabolism;
consistent with this hypothesis, mice in which CuZn-superoxide dismutase,
a major antioxidant enzyme, has been knocked out feature smaller skeletal
muscles and more rapid and extensive development of denervation than
wild-type controls ( Kostrominova et al., 2007; Larkin et al., 2011 ). The
reduction in mass and strength in the denervated muscle can be prevented
by a daily regime of electrical stimulations, delivered via implanted elec-
trodes ( Dow et al., 2004 ).
Denervation of skeletal muscle also occurs following spinal cord injury
( Biering-Sorensen et al., 2009; Dudley-Javoroski and Shields, 2008; Qin
et al., 2010 ). After the spinal cord injury, both Type I and Type II fibers'
atrophy and then the proportion of Type II fibers tend to increase; the
atrophied muscle is also gradually replaced by collagen and adipose tissue
( Biering-Sorensen et al., 2009 ). Spinal cord injury is associated with reduced
glucose tolerance ( Bauman et al., 1999 ). This may be due to loss of the mus-
cle, itself, which is a major glucose-utilizing tissue; additionally, the
increased fat content of the muscle likely contributes to impaired glucose
utilization in these patients ( Elder et al., 2004 ). Strategies which are being
considered to increase muscle mass include the use of anabolic steroids
( Wu et al., 2012 ) and direct electrical stimulation of the muscle ( Johnston
et al., 2011 ).
2.5. Sarcopenia and cachexia
Skeletal muscle mass diminishes with age, a phenomenon known as sar-
copenia. A component of sarcopenia is aging-associated denervation. How-
ever, sarcopenia typically begins as humans reach their 50s ( Deschenes,