Advances in molecular biology of hibernation in mammals

Abstract

Mammalian hibernation is characterized by profound reductions in metabolism, oxygen consumption and heart rate. As a result, the animal enters a state of suspended animation where core body temperatures can plummet as low as -2.9 degrees C. Not only can hibernating mammals survive these physiological extremes, but they also return to a normothermic state of activity without reperfusion injury or other ill effects. This review examines recent findings on the genes, proteins and small molecules that control the induction and maintenance of hibernation in mammals. The molecular events involved with remodeling metabolism, inducing hypothermia and maintaining organ function are discussed and considered with respect to analogous processes in non-hibernating mammals such as mice and humans. The advent of sequenced genomes from three distantly related hibernators, a bat, hedgehog and ground squirrel, provides additional opportunities for molecular biologists to explore the mechanistic aspects of this biological adaptation in greater detail.

Skeletal muscle mass and composition during mammalian hibernation

“…The hibernation state is characterized by long periods of inactivity, depressed metabolic rate, and fasting with increased reliance on fatty acids for metabolic fuel (Andrews, 2007). Most small mammal hibernators cycle through periodic torpor bouts with a duration of 5-40 days (mean 14 days) throughout a winter season (Geiser and Ruf, 1995).…”

Considerations on Temperature, Longevity and Aging

“…One possibility is that lowered CBT is a consequence of the reduced thyroid stimulating hormone (TSH) levels or is adaptive to the lower metabolic rate demonstrated at least in GH deficient mice [37]. No direct indication exists, to date, that the IGF-I pathway can modulate CBT, although it has been hypothesized that reduced insulin signaling may be one of the signals inducing hypothermia during hibernation [38]. Since the IGF-I pathway can regulate lifespan in poikilotherms, the insulin pathway is likely to act independently of CBT in controlling longevity and aging.…”

“…Importantly, studies on hibernation emphasized the close correlation between energy metabolism and CBT and identified some important mediators or regulators of this seasonal adaptation. These include the thyroid hormone derivative 3-iodiothyronamine, the 5'-adenosine monophosphate, the hormone grhelin and hydrogen sulfide gas, all of which are endogenous compounds that can induce hypothermia in mice (Reviewed in [38]). It is likely that further development in the field will identify molecules and pathways that are directly involved in the modulation of CBT.…”

Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals

“…reproduction, metabolism and migration) occurs widely in the animal kingdom (Farner, 1985), yet the underlying control mechanisms remain largely unknown. Hibernation represents one of the most extreme examples of seasonal physiological adaption, which is employed by a selective subset of mammals to conserve resources in cold or inhospitable environments (Andrews, 2007;Carey et al, 2003;Drew et al, 2007;Storey, 2010). Profound and precisely-controlled physiological changes occur during hibernation, enabling these mammals to endure dramatic drops in whole-body metabolism, heart and respiratory rates, and body temperature (Carey et al, 2003;Drew et al, 2007;Hampton et al, 2010;Heldmaier et al, 2004;Storey, 2010).…”