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Abstract

Mechanotransduction plays an important role in the regulation of muscle growth and metabolic signalling in striated muscle. Muscle disuse reduces mechanical input to the muscle, which results in a loss of muscle mass. Here I describe how titin's mechanically activated kinase domain affects muscle growth and metabolism via p62 and Akt signalling. I also demonstrate how changes in metabolic and growth signalling in hibernating grizzly bear help maintain muscle mass under conditions that induce muscle loss in humans and mice. I validated some of these changes in murine myotubes demonstrating that increasing non-essential amino acid levels, increasing Pdk4 levels or suppressing Serpinf1 has a positive effect on growth signalling that extends to non-hibernators.