Links Between Mammalian Hibernation and Longevity

In this open access paper, researchers review what is known of the commonalities between the biochemistry of hibernation and variations in longevity between mammalian species:

Many mammals employ strategies of metabolic rate depression - entry into winter hibernation, summer aestivation, or daily torpor - to allow them to extend their survival chances under extreme environmental conditions. Hibernation is perhaps the best known phenomenon and has been observed in eight different groups of mammal. Prior to hibernation, metabolic re-programming is initiated that includes hyperphagia in the late summer /early autumn, which results in massive weight gain due to increased fat storage in white adipose tissue. Animals then typically go through a number of "test drop" events of short torpor bouts at reduced body temperatures that appear to induce metabolic re-programming. Subsequently animals can initiate prolonged periods of torpor (days to weeks) with up to 95-99% reduction of basal metabolic rate as compared to the nonhibernating state, body temperatures that can fall to near 0°C, and metabolism switched over to a main reliance on lipid as the primary metabolic fuel for all organs. In addition to regulating metabolic fuel storage to support hypometabolism, hibernators are also faced with increased cellular stress during their torpor bouts. The decrease in respiration and heart rate during torpor creates an environment that is vulnerable to hypoxia/ischemia damage, whereas animals are also susceptible to oxidative stress during interbout arousals when metabolic rate and oxygen consumption increases massively to rewarm the animal back to euthermic conditions. As such, hibernators are incredible models to study the mammalian metabolic plasticity and stress resistance.

While metabolic rate depression and stress resistance have been shown to be the fundamental mechanisms that are required to support hibernation, they are also two of the most common cellular processes that have been shown to directly influence aging. While research in the aging field to date has utilized impressive genetic models that have uncovered many fundamental mechanisms that regulate aging and longevity in a conserved manner, research in non-traditional models such as hibernators can provide new insights into how environmentally-induced metabolic adaptations could influence aging and longevity. Hibernators may provide an advantage over traditional aging models as they naturally induce a hypometabolic state that triggers regulatory responses in a number of cellular signaling pathways which produce a significant increase in maximum lifespan when genetically altered.

Understanding the mechanisms of the hibernation response is important from a comparative point of view, since the molecular mechanisms that regulate torpor-mediated metabolic depression are likely conserved across other similar adaptive stress responses such as anoxia and hypoxia tolerance. However, the uniqueness of hibernation as an adaptation in mammals provides potential applications for biomedicine. In addition to its potential importance in aging and longevity, hibernators are great research models for (1) natural organ preservation, as they experience minimal tissue damage while maintained at body temperature just above freezing, and (2) insulin resistance, as they undergo reversible periods of insulin resistance and obesity without the detrimental effects seen in diabetic patients.


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