Is human hibernation possible?

The induction of hypometabolism in cells and organs to reduce ischemia damage holds enormous clinical promise in diverse fields, including treatment of stroke and heart attack. However, the thought that humans can undergo a severe hypometabolic state analogous to hibernation borders on science fiction. Some mammals can enter a severe hypothermic state during hibernation in which metabolic activity is extremely low, and yet full viability is restored when the animal arouses from such a state. To date, the underlying mechanism for hibernation or similar behaviors remains an enigma. The beneficial effect of hypothermia, which reduces cellular metabolic demands, has many well-established clinical applications. However, severe hypothermia induced by clinical drugs is extremely difficult and is associated with dramatically increased rates of cardiac arrest for nonhibernators. The recent discovery of a biomolecule, 5'-AMP, which allows nonhibernating mammals to rapidly and safely enter severe hypothermia could remove this impediment and enable the wide adoption of hypothermia as a routine clinical tool.

[1]  J. Doherty,et al.  The effects of short term cold storage upon ATP and 2,3-BPG levels in the blood of euthermic and hibernating thirteen-lined ground squirrels Spermophilus tridecemlineatus. , 1993, Comparative biochemistry and physiology. Comparative physiology.

[2]  H. Eltzschig,et al.  Physiological Roles of Vascular Nucleoside Transporters , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[3]  Y. Uchiyama.  A histochemical study of variations in the localization of 5′-nucleotidase activity in the acinar cell of the rat exocrine pancreas over the twenty-four hour period , 2004, Cell and Tissue Research.

[4]  Gerhard Heldmaier,et al.  Natural hypometabolism during hibernation and daily torpor in mammals , 2004, Respiratory Physiology & Neurobiology.

[5]  M. Lowe,et al.  Molecular mechanisms of rat and human pancreatic triglyceride lipases. , 1997, The Journal of nutrition.

[6]  H. Waterham,et al.  Metabolite transport across the peroxisomal membrane. , 2007, The Biochemical journal.

[7]  Michael R. Blackburn,et al.  Constant darkness is a circadian metabolic signal in mammals , 2006, Nature.

[8]  S. Williams,et al.  Metabolic effects of cold storage on livers from euthermic and hibernating Columbian ground squirrels. , 1996, Cryobiology.

[9]  I. Zucker,et al.  Photoperiod Modulates Torpor and Food Intake in Siberian Hamsters Challenged With Metabolic Inhibitors , 1999, Physiology & Behavior.

[10]  S. Wisniewski,et al.  Mild hypothermia improves survival after prolonged, traumatic hemorrhagic shock in pigs. , 2004, The Journal of trauma.

[11]  B. Barnes.  Freeze avoidance in a mammal: body temperatures below 0 degree C in an Arctic hibernator. , 1989, Science.

[12]  E. Newsholme,et al.  Activities and some properties of 5'-nucleotidase, adenosine kinase and adenosine deaminase in tissues from vertebrates and invertebrates in relation to the control of the concentration and the physiological role of adenosine. , 1978, The Biochemical journal.

[13]  W. Frederiks,et al.  Diurnal variation in 5′-nucleotidase activity in rat liver , 1987, Histochemistry.

[14]  A. Lehninger.  Biochemistry: The Molecular Basis of Cell Structure and Function , 1970 .

[15]  M. Lowe,et al.  Pancreatic triacylglycerol lipase in a hibernating mammal. II. Cold-adapted function and differential expression. , 2003, Physiological genomics.

[16]  J. Encinas,et al.  Identification and Characterization of a Cell-Surface Receptor, P2Y15, for AMP and Adenosine* , 2004, Journal of Biological Chemistry.

[17]  H. Heller,et al.  Sleep and circadian rhythms in mammalian torpor. , 2004, Annual review of physiology.

[18]  M. Roth,et al.  H2S Induces a Suspended Animation–Like State in Mice , 2005, Science.

[19]  J. Ilkiw,et al.  Surface-induced hypothermia in dogs: 19 cases (1987-1989). , 1993, Journal of the American Veterinary Medical Association.

[20]  G. Burnstock,et al.  The recently deorphanized GPR80 (GPR99) proposed to be the P2Y15 receptor is not a genuine P2Y receptor. , 2005, Trends in pharmacological sciences.

[21]  B. Johansson.  The hibernator heart--nature's model of resistance to ventricular fibrillation. , 1996, Arctic medical research.

[22]  G Burnstock,et al.  Receptors for purines and pyrimidines. , 1998, Pharmacological reviews.

[23]  K. Storey,et al.  Enzymes of adenylate metabolism and their role in hibernation of the white-tailed prairie dog, Cynomys leucurus. , 2000, Archives of biochemistry and biophysics.

[24]  J. D. Sharer.  The adenine nucleotide translocase type 1 (ANT1): A new factor in mitochondrial disease , 2005, IUBMB life.

[25]  Jack A Boulant.  Neuronal basis of Hammel's model for set-point thermoregulation. , 2006, Journal of applied physiology.

[26]  H. Stephan,et al.  Freeze Avoidance in a Mammal: Body Temperatures Below 00C in an Arctic Hibernator , 1989 .

[27]  W. Walker,et al.  Nucleotide supplements alter proliferation and differentiation of cultured human (Caco-2) and rat (IEC-6) intestinal epithelial cells. , 1993, The Journal of nutrition.

[28]  Stephen A Baldwin,et al.  Nucleoside transporters: from scavengers to novel therapeutic targets. , 2006, Trends in pharmacological sciences.

[29]  I. Zucker,et al.  Reduced glucose availability induces torpor in Siberian hamsters. , 1994, The American journal of physiology.

[30]  C. Lluis,et al.  ATP-Sensitive K+ Channels Regulate the Concentrative Adenosine Transporter CNT2 following Activation by A1 Adenosine Receptors , 2004, Molecular and Cellular Biology.

[31]  J. Lindsley,et al.  Nutrient sensing and metabolic decisions. , 2004, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.