Abstract
Muscle atrophy is one of the main characteristics of human ageing and physical inactivity, with resulting adverse health outcomes. To date, there are still no efficient therapeutic strategies for its prevention and/or treatment. However, during hibernation, bears exhibit a unique ability for preserving muscle in conditions where muscle atrophy would be expected in humans. Therefore, our objective was to determine whether there are components of bear serum which can control protein balance in human muscles. In this study, we exposed cultured human differentiated muscle cells to bear serum collected during winter and summer periods, and measured the impact on cell protein content and turnover. In addition, we explored the signalling pathways that control rates of protein synthesis and degradation. We show that the protein turnover of human myotubes is reduced when incubated with winter bear serum, with a dramatic inhibition of proteolysis involving both proteasomal and lysosomal systems, and resulting in an increase in muscle cell protein content. By modulating intracellular signalling pathways and inducing a protein sparing phenotype in human muscle cells, winter bear serum therefore holds potential for developing new tools to fight human muscle atrophy and related metabolic disorders.
Highlights
Muscle disuse atrophy is common in humans during immobilization, bedrest, spaceflight, denervation, cancer, and ageing, and represents a major health issue[1,2,3], and is observed in a number of non-human models used for atrophy studies[4]
To evaluate the ability of bear serum to impact human muscle cell protein content, we first incubated quiescent differentiated polynucleated myotubes with bear serum collected in winter during hibernation and in summer during their active period
While no difference could be observed between FBS and summer bear serum (SBS) conditions, the winter bear serum (WBS) treatment induced a significant increase in muscle cell surface area (+21.7 ± 7.2% p = 0.015) compared to SBS, indicating higher protein content
Summary
Muscle disuse atrophy is common in humans during immobilization, bedrest, spaceflight, denervation, cancer, and ageing, and represents a major health issue[1,2,3], and is observed in a number of non-human models used for atrophy studies[4]. A very low loss in protein content (from 4% to 17%) is reported in early winter, and this value remains uniquely stable during the following 3–4 months, whereas muscle and fibre cross-sectional area is preserved[13,14,15], and muscle strength only decreases by 23%15. The direct corollary is the possible role of still unknown humoral factors in controlling bear muscle adaptive responses to hibernation In support of this view, winter bear plasma has been reported to induce a 40% decrease in the net proteolytic rate in isolated rat muscles[20], indicating the presence of circulating factors possibly able to trigger protein sparing during hibernation. Our results highlight how serum from hibernating bears is able to trigger trans-species effects, being a potential source for new therapeutic molecules to fight human muscle atrophy and associated metabolic disorders
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