Inhibiting Myostatin Increases Muscle Mass in Old Mice

A range of different manipulations of myostatin have been shown to safely and significantly increase muscle mass and strength in mice. Some rare natural myostatin mutants exist in our species and other larger mammals. All in all it seems like a promising line of research to ameliorate age-related muscle loss, whether or not it rises to the level of diagnosis as sarcopenia. This doesn't address the underlying causes, but it could greatly increase the buffer of muscle tissue to resist those causes: a patch, but not a bad patch, given the large degree to which muscle mass is gained in these experiments.

Mammalian aging is accompanied by a progressive loss of skeletal muscle, a process called sarcopenia. Myostatin, a secreted member of the transforming growth factor-β family of signaling molecules, has been shown to be a potent inhibitor of muscle growth. Here, we examined whether muscle growth could be promoted in aged animals by antagonizing the activity of myostatin through the neutralizing activity of the myostatin propeptide.

We show that a single injection of an AAV8 virus expressing the myostatin propeptide induced an increase in whole body weights and all muscles examined within 7 weeks of treatment. Our cellular studies demonstrate that muscle enlargement was due to selective fiber type hypertrophy, which was accompanied by a shift toward a glycolytic phenotype. Our molecular investigations elucidate the mechanism underpinning muscle hypertrophy by showing a decrease in the expression of key genes that control ubiquitin-mediated protein breakdown. Most importantly, we show that the hypertrophic muscle that develops as a consequence of myostatin propeptide in aged mice has normal contractile properties. We suggest that attenuating myostatin signaling could be a very attractive strategy to halt and possibly reverse age-related muscle loss.



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