The maintenance of skeletal muscle mass and function is critical for healthy aging. Muscle
loss with disuse, termed muscle disuse muscle atrophy, leads to impaired functional capacity,
the onset of insulin resistance, as well as a heightened risk for morbidity and mortality.
With advancing age there is a chronic wasting of muscle. This is especially true in women,
where rapid rates of decline in muscle mass and greater anabolic resistance are experienced
around the time of menopause, despite higher protein synthesis rates. As women have a longer
life expectancy, they are particularly venerable to age-related frailty and morbidity.
Skeletal muscle protein turnover serves to maintain the optimal function of proteins and also
provides plasticity of the tissue during altered demands such as during increased loading or
unloading of the muscle. Reduced periods of physical activity also have a similar, albeit
milder, impact on skeletal muscle and most, people will likely experience multiple bouts of
skeletal muscle disuse during their lifetime from which some, particularly older adult women,
will fail to fully recover. Thus, muscle disuse atrophy is a significant and continuing
problem as reclamation of lost muscle mass, strength/function, and potentially metabolic
health (particularly insulin-induced glucose disposal), following disuse is oftentimes
incomplete and may be further exacerbated after menopause.
Previous evidence has demonstrated that in the loss of muscle mass is less pronounced in
post-menopausal women when receiving hormone replacement therapy. Skeletal muscle has
estrogen-β-receptors on the cell membrane, in the cytoplasm and on the nuclear membrane, and
therefore a direct mechanistic link between low estrogen levels and a decrease MPS.
Interestingly, despite higher rates of protein synthesis, older women still lose muscle mass
with advancing age. It has been suggested that the negative muscle protein balance is due to
an enhanced rate of MPB. Insulin is a potent inhibitor of MPB and estrogen has been shown to
enhance insulin sensitivity in skeletal muscle. However, to our knowledge, no study has
examined the efficacy of estrogen supplementation to attenuate the losses of skeletal muscle
mass and function during a period of disuse. The findings of this investigation may yield
critical data for those who wish to combat skeletal muscle disuse atrophy, particularly after
menopause.