Tuesday, January 27, 2015

Real-Life Superheroes Look Like What?!

Written by Tracy Mulholland

Hairless, tiny, and nearly blind, the naked mole rat (Heterocephalus glaber) has grasped the attention of scientists and laymen alike. They may be visually unappealing, but their physiology is entrancing. Despite being a mammal, this odd rodent is a thermoconformer, can withstand hypoxic (=low oxygen) environments, and is apparently resistant to cancer. Could it be that this wrinkly eye sore is the epitome of physiological finesse? 
Naked mole rats live in underground burrows with inadequate oxygen and upwards of 80 of their family members (yikes!). However, It is these same strenuous conditions that allow for the odd mammals to be thermoconformers (i.e. their temperature varies with that of the environment). Living in subterranean tunnel systems means relatively stable ambient temperatures of around 30ÂșC. Living with dozens of other mole rats also has its benefits; one of which is a behavior familiar to all of us: group huddling. Cuddling up to the wrinkly, bare skin of another naked mole rat decreases the surface area to volume ratio. Less exposed skin means a reduction in the amount of heat lost to the surroundings, helping to maintain their internal body temperature.

            If the thought of living in dark underground tunnels with countless relatives nearby (or on top of) you doesn’t make you uncomfortable, add the thought of hyperventilation. Hyperventilation occurs when low levels of carbon dioxide are detected in the blood. When faced with inadequate oxygen supplies, most mammals (including us) attempt to increase oxygen supplies by increasing inhalation (i.e. me trying to run up a hill).  Conversely, the picturesque naked mole rat decreases its breathing when facing hypoxia, lowering both their ventilation and their metabolic rate by 70%. Their ability to equally match their ventilation rate with their metabolic rate, combined with their high-oxygen-affinity hemoglobin and low basal metabolic rate, allow them to withstand chronic hypoxic environments.

In addition to being able to survive (and function) in low oxygen environments with exceedingly low metabolic rates, they are unaffected by certain types of pain. Researches have noticed that H. glaber is insensitive to acid and capsaicin (the active component in chill peppers- ouch!). When applied to the skin, these irritants usually produce inflammation, burning sensations and pain- But not when applied to the seemingly impenetrable skin of the amazing naked mole rat. Researches used electrophysiology to study the rodent’s response mechanism when exposed to these pain-producing substances. In most “normal” (non-superhero) vertebrates, special sensory neurons called nociceptors (=pain receptors) transmit the pain signal to the spinal cord. Hyperalgesia (=temporary increased sensitivity) caused by the damage of these nerves usually ensues.  This same transduction of signal when exposed to chemical irritants such as acid and capsaicin does not occur in the naked mole rat. 




 While it appears thus far that naked mole rat pain receptors lack the ability to detect acid altogether, the receptors do respond to capsaicin. However, the signaling pathway is different. Instead of signaling a pathway to indicate pain, the nerves go instead to the “touch” region of the spinal cord. Thus, naked mole rats are able to maintain that adorable, ecstatic looking face even when chill pepper irritants are rubbed on their skin.


If you are still not convinced these small rodents should be wearing tiny red capes on their backs, let's look at their longevity. A species maximum lifespan is, with some exceptions, relative to its body size (i.e. bigger = longer lived). The naked mole rat is approximately 8 centimeters in size and weighs less than 40 grams. Despite its puny size, these animals can live up to thirty years! (For reference, mice live approximately four years).


Their long lifespan would be slightly less coveted if it weren't for  another physiological anomaly: they show little signs of aging. Yes, they may look like they’re eighty their entire life, but their muscles show no signs of deterioration and breeding females remain fertile until death. Even more surprising, naked mole rats are impervious to cancer. Researches have just recently discovered a mechanism for their incredible longevity and resilience, and it has to do with the secretion of a gooey substance from their fibroblasts (another lovely image for you). Fibroblasts, cells typically found in connective tissue, secrete high-molecular-mass hyaluronan (HA), a complex sugar.  The high amount of large HA produced by naked mole rats surround their cells, suppressing tumor formation. Though it is thought high HA abundance originally evolved for skin elasticity, it also makes this rodent one step closer to being a real-life superhero.


* For a brief and hilarious summary of the aforementioned points, watch this 3 minute video:

 References:


Buffenstein, R. 2008. Negligible senescence in the longest living rodent,
the naked mole-rat: insights from a successfully aging species. Journal of Comparative Physiology B 178:439–445.

Larson, J., K.L. Drew, L.P. Folkow, S. L. Milton, and T.J. Park. 2014. No oxygen? No problem! Intrinsic brain tolerance to hypoxia in vertebrates. The Journal of Experimental Biology 217: 1024-1039.

Pamenter, M.E., Y.A. Dzal and W.K. Milsom. 2014. Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia. Proceedings of the Royal Society B 282:20141722.

Park, T.J., Y. Lu, R. Juttner, E.S.J. Smith, J. Hu, A. Brand, C. Wetzel, N. Milenkovic, B. Erdmann, P.A. Heppenstall, C. E. Laurito, S.P. Wilson, and G.R. Lewin. 2013. Selective inflammatory pain insensitivity in the African Naked Mole Rat (Heterocephalus glaber). PloS Biology 6:e13

Shlomo, Y. and R,  Buffenstein. 1991. Huddling Behavior Facilitates Homeothermy in the Naked Mole Rat Heterocephalus glaber. Physiological Zoology 64:871-884.

Tian, X., J. Azpurua, C. Hine, A. Vaidya, M. Myakishev-Rempel, J. Ablaeva, Z., Mao, E. Nevo, V. Gorbunova and A. Seluanov. 2013. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499: 346–349

“Naked mole-rats don't feel the burn” Anna Petherick; Published online 28 January 2008 | Nature | doi:10.1038/news.2008.535 <http://www.nature.com/news/2008/080128/full/news.2008.535.html

“The weird and wonderful world of the naked mole rat” Tim Adams 13 July 2013<http://www.theguardian.com/science/2013/jul/14/naked-mole-rat-cancer-research >


Images: 





Video:



“True Facts About The Naked Mole Rat” <http://www.youtube.com/watch?v=eHi9FvUPSdQ



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