Myostatin levels in skeletal muscle of hibernating ground squirrels

Bone mass and skeletal muscle mass are controlled by factors such as genetics, diet and nutrition, growth factors and mechanical stimuli. Whereas increased mechanical loading of the musculoskeletal system stimulates an increase in the mass and strength of skeletal muscle and bone, reduced mechanical loading and disuse rapidly promote a decrease in musculoskeletal mass, strength and ultimately performance (i.e. muscle atrophy and osteoporosis). In stark contrast to artificially immobilised laboratory mammals, animals that experience natural, prolonged bouts of disuse and reduced mechanical loading, such as hibernating mammals and aestivating frogs, consistently exhibit limited or no change in musculoskeletal performance. What factors modulate skeletal muscle and bone mass, and what physiological and molecular mechanisms protect against losses of muscle and bone during dormancy and following arousal? Understanding the events that occur in different organisms that undergo natural periods of prolonged disuse and suffer negligible musculoskeletal deterioration could not only reveal novel regulatory factors but also might lead to new therapeutic options. Here, we review recent work from a diverse array of species that has revealed novel information regarding physiological and molecular mechanisms that dormant animals may use to conserve musculoskeletal mass despite prolonged inactivity. By highlighting some of the differences and similarities in musculoskeletal biology between vertebrates that experience disparate modes of dormancy, it is hoped that this Review will stimulate new insights and ideas for future studies regarding the regulation of atrophy and osteoporosis in both natural and clinical models of muscle and bone disuse.

Section: Regulation Of Protein Synthesismentioning

confidence: 79%

Prevention of muscle wasting and osteoporosis: the value of examining novel animal models

Reilly

Franklin

2016

“…In thirteen-lined ground squirrels, myostatin protein levels in mixed hindlimb muscle were generally constant throughout torpor as compared with controls, but rose significantly during arousal (Brooks et al, 2011). Also, during arousal from hibernation, many hibernators undergo shivering thermogenesis, during which there is vigorous activity of muscles, which may also play a role in maintaining muscle mass (Lee et al, 2010).…”

Section: Skeletal Muscle Sizementioning

confidence: 94%

“…During torpor bouts, hibernators exhibit no discernible movement, yet previous studies on the effects of hibernation on skeletal muscle have demonstrated relatively low levels of muscle atrophy when compared with nonnatural models of muscle disuse (Musacchia et al, 1988;Hudson and Franklin, 2002;Shavlakadze and Grounds, 2006). A range of mechanisms are thought to contribute to this resistance to skeletal muscle atrophy, including increased levels of antioxidants (Hudson and Franklin, 2002;Allan and Storey, 2012), reduced levels of myostatin (Braulke et al, 2010;Brooks et al, 2011;Nowell et al, 2011) and the regulation of transcription factors that transcribe genes associated with muscle performance (Tessier and Storey, 2010). Higher levels of antioxidants, such as glutathione and superoxide dismutase, are thought to counter the effects of reactive oxygen species (ROS), reducing cellular damage and potential muscle atrophy (Carey et al, 2003;Powers et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The effects of hibernation on the contractile and biochemical properties of skeletal muscles in the thirteen-lined ground squirrel, Ictidomys tridecemlineatus

James

Staples

Brown

et al. 2013

Self Cite

SUMMARYHibernation is a crucial strategy of winter survival used by many mammals. During hibernation, thirteen-lined ground squirrels, Ictidomys tridecemlineatus, cycle through a series of torpor bouts, each lasting more than a week, during which the animals are largely immobile. Previous hibernation studies have demonstrated that such natural models of skeletal muscle disuse cause limited or no change in either skeletal muscle size or contractile performance. However, work loop analysis of skeletal muscle, which provides a realistic assessment of in vivo power output, has not previously been undertaken in mammals that undergo prolonged torpor during hibernation. In the present study, our aim was to assess the effects of 3months of hibernation on contractile performance (using the work loop technique) and several biochemical properties that may affect performance. There was no significant difference in soleus muscle power output-cycle frequency curves between winter (torpid) and summer (active) animals. Total antioxidant capacity of gastrocnemius muscle was 156% higher in torpid than in summer animals, suggesting one potential mechanism for maintenance of acute muscle performance. Soleus muscle fatigue resistance was significantly lower in torpid than in summer animals. Gastrocnemius muscle glycogen content was unchanged. However, state 3 and state 4 mitochondrial respiration rates were significantly suppressed, by 59% and 44%, respectively, in mixed hindlimb skeletal muscle from torpid animals compared with summer controls. These findings in hindlimb skeletal muscles suggest that, although maximal contractile power output is maintained in torpor, there is both suppression of ATP production capacity and reduced fatigue resistance.

“…In ground squirrels, muscles exhibiting the least amount of atrophy tend to also have the greatest depression of myostatin and FoxO (Nowell et al, 2011). When examined on a finer scale, however, myostatin levels appear to increase during arousal periods along with downstream transcription factors Smad 2 and Smad 3 (Brooks et al, 2011), suggesting a potential role in increasing protein turnover during interbout arousal periods (Table 2).…”

Section: Myostatinmentioning

confidence: 99%

Skeletal muscle mass and composition during mammalian hibernation

Cotton

2016

Hibernation is characterized by prolonged periods of inactivity with concomitantly low nutrient intake, conditions that would typically result in muscle atrophy combined with a loss of oxidative fibers. Yet, hibernators consistently emerge from winter with very little atrophy, frequently accompanied by a slight shift in fiber ratios to more oxidative fiber types. Preservation of muscle morphology is combined with downregulation of glycolytic pathways and increased reliance on lipid metabolism instead. Furthermore, while rates of protein synthesis are reduced during hibernation, balance is maintained by correspondingly low rates of protein degradation. Proposed mechanisms include a number of signaling pathways and transcription factors that lead to increased oxidative fiber expression, enhanced protein synthesis and reduced protein degradation, ultimately resulting in minimal loss of skeletal muscle protein and oxidative capacity. The functional significance of these outcomes is maintenance of skeletal muscle strength and fatigue resistance, which enables hibernating animals to resume active behaviors such as predator avoidance, foraging and mating immediately following terminal arousal in the spring.