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The Bare Facts of Naked Mole Rats

posted Sep 9, 2014, 1:06 AM by Al Liance   [ updated Sep 11, 2014, 6:20 PM by Virginie MOURNETAS ]
By Shaun Calvet

The naked mole rat is becoming increasingly popular as a model organism for scientists to study, but what is a naked mole rat? And why are scientists studying them anyway? As I am one of these scientists, I feel I should explain.

Firstly,  its name may be a little misleading, because the naked mole rat (NMR) isn’t actually naked. Its body is covered in fine hairs and it isn’t a mole or a rat, and is indeed more closely related to porcupines or guinea pigs. The NMR lives in the horn of Africa (Somalia, Kenya and Ethiopia) and is subterranean. They dig large networks of tunnels searching for roots and tubers which they feed on. A single NMR would have a hard time finding food this way by itself; fortunately, they have evolved to form complex eusocial colonies. This means that there is a single breeding female per colony that supresses the reproductive potential of all other members of the colony, apart from two to three breeding males. The non-breeding mole rats can be split into two different sub types; these are the workers that are smaller individuals and have large teeth that they use to dig and expand the burrow, and soldiers that are larger and defend the colony from snakes that can infiltrate the burrow. This kind of hierarchy with a single breeding female is something we tend to associate with bees or ants, but NMRs are mammals like us. Interestingly,  there is also a pecking order between individuals: when two NMRs meet in a tunnel and wish to pass each other, the individual that is higher in the pecking order gets to walk over the top of the other.

 Figure 1. Heterocephalus glaber aka the naked mole rat is a long lived and cancer resistant rodent that is also adorable.

Mole rat colonies can be up to 300 individuals in size, and hence, careful organisation of the burrow is vital. The burrows are incredibly complex in their structure, with ‘highways’ as well as turnaround areas and escape routes.  Even more  impressive are the toilet burrows that the NMR almost exclusively use to prevent the incidence of disease in the colony.

Living in burrows and colonies not only protects against predation,  but the use of toilet burrows also reduces  the incidence of disease. This means NMRs are less likely to be killed early in life, and therefore, they have evolved to live longer, up to 32 years old in fact (1). When compared to the similar sized mouse that only lives for approximately 4 years, the lifespan of NMRs are huge.  Indeed, the long lifespan of NMRs goes against the general trend seen in nature, in that larger animals typically live much longer (Figure 2). Animals that live longer then we would expect based on their body size are considered long lived.

Both humans and NMRs live much longer than we would expect based on body mass.

 Figure 2. This graph shows that as body mass of a mammalian species increases so does its maximum lifespan. H. s. stands for Homo sapien. H. g. stands for Heterocephalus glaber aka the naked mole rat. Both of these species are living  much longer than we would expect based on their body size. The lifespan we would expect based on body size is denoted by the line that marks the trend of life span in nature with regards to body mass (2).
 

The NMR may not live as long as humans (our record is 122 years old), but they do possess other survival advantages over us. A particularly important advantage is that NMRs seem to be cancer resistant. At least, cancer has yet to be observed in any specimen, not even ‘old man’, the NMR that set the species lifespan record of 32 years old (2). This cancer resistance and long lifespan could arise from a number of different physiological features found in the NMR.

It is well understood that a reduction in cell efficiency can contribute to aging, and this is a major risk factor for many forms of cancer (3). Indeed, studies of how cells in the NMR make proteins (the cell’s building blocks) have shown that compared to mouse cells, NMR cells are much more efficient, and make less mistakes during protein translation. This means that less defective proteins are made that would otherwise clutter up the cell, waste resources and generally impede the cell’s usual activities.

DNA damage is also considered to be one of the leading factors in both aging and cancer (5). Interestingly, NMR cells are more resistant to many forms of DNA damage than mouse cells (4). Studies have shown that when NMR cells are treated with DNA damaging compounds, they also seem to wait longer before continuing to grow, as if making extra sure that all of the DNA has been repaired. Again, this is important in preventing the production of defective proteins.

Finally, NMR cells produce a thick sticky substance called hyaluronan. This substance is made in both humans and mice, but in NMR, the molecule is over 5 times larger and is hence called high molecular mass hyaluronan (HMHA) (6). This makes the substance thicker, and may well allow it to physically block the growth and spread of cancerous cells. It may also interact with the cell’s surface to activate anti-cancer mechanisms within the cell. Malignant transformations (affecting genes in such a way that the cell becomes cancerous), that produce cancer in mice cells fail to do so in NMR cells unless they are modified in such a way that HMHA is no longer produced (6).

In conclusion, not only are NMRs adorable, but they are also pretty incredible little creatures. Their long life span and cancer resistance makes them an obvious target for researchers, who hope to one day apply what they learn in NMRs to humans. And who knows, this could lead to exciting discoveries of how to prevent cancer, increase our resistance to DNA damage and maybe even age slower.


References

  1. Buffenstein R. Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species. J Comp Physiol B 2008; 178: 439–445. 
  2. Naked Mole-Rat Genome Resource 2014. http://naked-mole-rat.org 
  3. Jorge Azpurua, Zhonghe Ke, Iris X. Chen, Quanwei Zhang, Dmitri N. Ermolenkoc, Zhengdong D. Zhangb, Vera Gorbunova, and Andrei Seluanov. Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage. 2013. PNAS vol. 110 no. 43. 
  4. Kaitlyn N. Lewis, James Mele, Peter J. Hornsby , Rochelle Buffenstein. Stress Resistance in the Naked Mole Rat: The Bare Essentials – A Mini-Review. 2012. Gerontology 2012;58:453–462. 
  5. De Magalhaes, J.P. (2013). How ageing processes influence cancer. Nature Reviews Cancer 13, 357-365. 
  6. Xiao Tian, Jorge Azpurua, Christopher Hine, Amita Vaidya, Max Myakishev-Rempel, Julia Ablaeva, Zhiyong Mao, Eviatar Nevo, Gorbunovan, and Andrei Seluanov. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. 2013. Nature 499Pages:, 346–349