Abstract
The winter months are challenging for many animal species, which often enter a state of dormancy or hypometabolism to “wait out” the cold weather, food scarcity, reduced daylight, and restricted mobility that can characterize the season. To survive, many species use metabolic rate depression (MRD) to suppress nonessential metabolic processes, conserving energy and limiting tissue atrophy particularly of skeletal and cardiac muscles. Mammalian hibernation is the best recognized example of winter MRD, but some turtle species spend the winter unable to breathe air and use MRD to survive with little or no oxygen (hypoxia/anoxia), and various frogs endure the freezing of about two-thirds of their total body water as extracellular ice. These winter survival strategies are highly effective, but create physiological and metabolic challenges that require specific biochemical adaptive strategies. Gene-related processes as well as epigenetic processes can lower the risk of atrophy during prolonged inactivity and limited nutrient stores, and DNA modifications, mRNA storage, and microRNA action are enacted to maintain and preserve muscle. This review article focuses on epigenetic controls on muscle metabolism that regulate MRD to avoid muscle atrophy and support winter survival in model species of hibernating mammals, anoxia-tolerant turtles and freeze-tolerant frogs. Such research may lead to human applications including muscle-wasting disorders such as sarcopenia, or other conditions of limited mobility.
Highlights
This review covers epigenetic changes in hibernation, freeze tolerance, and hypoxia/anoxia as it relates to muscle tissue (Figure 2)
Increases in miR-27, miR-29, and miR-33 in U. arctos skeletal muscle may suggest that both glucose uptake and fatty acid oxidation are suppressed in hibernating bears, signifying a miRNA-mediated switch in fuel usage during the winter [31]
Since miRNA expression in skeletal muscle suggests that AMPK is downregulated, thereby promoting fatty acid metabolism and a shift away from glucose uptake, an explanation may be that glucose is reprioritized for the brain during hypoxia, an organ very sensitive to ATP limitation and this can be mitigated, in part, by reducing glucose uptake and use by muscle cells
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Since the discovery of the first miRNAs, let-7 and lin-4 in 1993, hundreds of miRNAs have been identified across animal and plant species, all of which exhibit very high conservation between species Given such high conservation among vertebrates, and the possession of unique features that make miRNA ideal for implementing reversible, transient phenotypes, miRNAs represent a robust mode of posttranscriptional regulation that plays a crucial and dynamic role in allowing organisms to make rapid changes to mRNA translation in response to diverse signals including rapidly changing environmental conditions. Part 4 is about transcriptional and translational suppression, a common result of epigenetic changes in muscle tissue given that many animals are largely immobile in their winter-survival states This occurs mostly during freeze tolerance and hypoxia/anoxia exposure. This review covers epigenetic changes in hibernation, freeze tolerance, and hypoxia/anoxia as it relates to muscle tissue (Figure 2)
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