Molecular interactions underpinning the phenotype of hibernation in mammals

Mammals maintain a constant warm body temperature, facilitating a wide variety of metabolic reactions. Mammals that hibernate have the ability to slow their metabolism, which in turn reduces their body temperature and leads to a state of hypothermic torpor. For this metabolic rate reduction to occur on a whole-body scale, molecular interactions that change the physiology of cells, tissues and organs are required, resulting in a major departure from normal mammalian homeostasis. The aim of this Review is to cover recent advances in the molecular biology of mammalian hibernation, including the role of small molecules, seasonal changes in gene expression, cold-inducible RNA-binding proteins, the somatosensory system and emerging information on hibernating primates. To underscore the importance of differential gene expression across the hibernation cycle, mRNA levels for 14,261 ground squirrel genes during periods of activity and torpor are made available for several tissues via an interactive transcriptome browser. This Review also addresses recent findings on molecular interactions responsible for multi-day survival of near-freezing body temperatures, single-digit heart rates and a slowed metabolism that greatly reduces oxygen consumption. A better understanding of how natural hibernators survive these physiological extremes is beginning to lead to innovations in human medicine.