Naked mole rats are small, hairless, subterranean rodents that, like many other rodent species, live in their own colonies, digging burrows for the whole clan, spending most of the time foraging for seeds and small nuts. What makes the naked mole rats so special? Well along with their long lifespan, being the only cold-blooded mammal, lacking pain sensitivity, and an impressive ability to survive in extremely low levels of oxygen, they also have extreme resistance to cancer. In other words, naked mole rats are immune to cancer.
Cancer immunity
Previously, scientists believed that naked mole rats have a heightened resistance because their healthy cells couldn't be converted into cancerous cells and tumors. There have been various experiments to inject the NMR cells with modified viruses to trigger cancer but to no avail. A significant study that details the cell structure of the naked mole rat was a research experiment carried by Vera Gorbuvera and Andrei Seluanov of the University of Rochester.
Their study shifted focus to a gooey-like substance called HMW-HA which seemed to clog in the naked mole rat culture. This substance was present at this amount and viscosity at any other media of other mammals. Their research showed that when this chemical was taken away, the cells suddenly became susceptible to tumors. They even attempted to shut down the gene that encodes for HMW-WA before inserting the cancer-causing virus - they started multiplying rapidly and formed into tumors. suggesting a correlation between this and its resistance. Furthermore, the gene HAS2 identified to be responsible for making HMW-HA is different from all other mammals. They also recycle HMW-HA at a much slower pace which leads to its accumulation.
In their previous research, they showed that the p16 gene in naked mole rats prevented the cells from multiplying rapidly when too many of them crowded together. This study has fortunately been built to suggest that HMW-HA is a chemical that stimulates the anti-cancer response of the p16. The study finally concluded that HWA-HA was responsible for sending a signal to cells through the C44 receptor to stop them from turning cancerous.
However, this has been proven false by a study published by the University of Cambridge in July 2020 which stated that this is not the case.
The study analyzed 79 different cell lines grown from the intestine, kidney, lung, and skin tissue taken from 11 individual mole rats. They infected mole rat cells with modified viruses to introduce cancer-causing genes. Contradicting the hypothesis that they shouldn't be able to transform into cancerous cells, the cells begin to rapidly multiply and form colonies in the lab, and when injected into mice, were able to form tumors. This led to the conclusion that their cells can become cancerous, just like in other rodent species.
So why is it that NMRs are immune to cancer even though they can produce cancerous cells? The study had suggested that it is the interactions within the microenvironment (the complex system of cells and molecules surrounding a cell, including the immune system) that prevent cancer from developing into a tumor.
However, this was redacted by scientists at the university of Rochester responsible for the 2013 study, who argued that the new study concluded different results was because they injected “artificially high levels” of cancer-causing genes which eventually forced the mice to get cancer.
A lot of our current cancer research is focused on animals that are prone to cancer but these initial discoveries may pave a way to derive more knowledge and research from animals that are “cancer-proof”. Due to the similarities in the human genome between NMRs and humans, NMRs have made a pretty efficient model to study and evaluate the cancer resistance mechanisms for the past decade. It certainly helps that there are a lot of pre-existing data in cancer within mice as a lot of the data show house mouse models fundamentally get cancer like humans, so there’s not that big of a biological leap.
It helps underpin specific mechanisms which contribute to this cancer resistance and uses further data to successfully translate the same response in a human body. So evidently, understanding this immunity and resistance can help scientists gain a better understanding of the early stages of cancer and hence find more ways to treat and detect it in humans.
Other marvels: Surviving without oxygen
Unlike other known mammals, NMRs do not die when their brain cells are deprived of oxygen. They are known to survive for hours in very low levels of oxygen- and 18 minutes without any oxygen. Its fellow mice can die 20 seconds after not receiving any oxygen. Previous studies have shown that they conserve energy by reducing their breathing rate and dramatically slowing their pulse, but it was still confusing how their brain cells never sustained any lasting brain damage due to the low levels of oxygen.
Recent studies suggest that when NMRs are deprived of oxygen they switch from a glucose-based system to a fructose-based system, which does not require oxygen and can be turned into energy anaerobically. Generally more common in plants, they are now the known animal species to be able to respire in this way.
This even raises the potential question: can human cells also survive without oxygen? If human cells could also adapt this rearrangement in metabolism, from glucose to fructose, doctors might be able to save critical organs in the event of a stroke.
Other marvels: resistance to aging
The naked mole rat is the longest-lived rodent species, reaching 32 years, 10 times longer than that of a mouse. And for 80% of its lifespan, it shows no signs of aging while retaining the ability to reproduce with little increase of the age-specific hazard of mortality, unlike every other mammalian species.
Comparative biologist, Rochelle Buffenstein who had studied the animals for three decades and has collected lots of analyzed data about each of the animals in her care, mentioned that it contradicts Gompertz's law of aging. The Gompertz law was coined by British mathematician Benjamin Gompertz who stated that the risk of dying increases exponentially with age. For humans, the figure stands at doubling every 8 years after we reach 30. this theory has been true for all known mammalian animals- except the naked mole rat.
Buffenstien concluded with her data, that once NMRs reach a maturity of 6 months, their chance of dying decreases to 1 in 10000, and manages to stay like that for most of their lifetime. Further studies have detailed the reasons being their very active DNA repair and high levels of proteins that help other proteins fold correctly (chaperones). These high levels act to prevent or correct damage caused by misfolding.
However, this is still a point of debate as some scientists have rejected the idea of NMRs being non-aging animals, stating that more information and data patterns need to be collected, as well as more detailed biological research to show aging happens in NMRs.
We are just now beginning to fully understand the biological mechanisms of mammalian species, and naked mole rats are playing a significantly active role in it. Wherever further research leads, it seems that these small rodent species might just open brand new doors in the future medical field for us.
Citations:
NewsCenter. (2013). Naked Mole Rats Cancer-resistant Chemical ID’d. [online] Available at: https://www.rochester.edu/newscenter/naked-mole-rats-cancer-resistant-chemical-ided/ [Accessed 14 Mar. 2021].
A Homely Rodent May Hold Cancer-Fighting Clues (Published 2013). (2021). The New York Times. [online] Available at: https://www.nytimes.com/2013/06/19/science/a-homely-rodent-may-hold-cancer-fighting-clues.html?_r=2& [Accessed 14 Mar. 2021].
J Graham Ruby, Smith, M. and Buffenstein, R. (2018). Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age. [online] eLife. Available at: https://elifesciences.org/articles/31157 [Accessed 14 Mar. 2021].
Laura Elizabeth Lansdowne (2020). What Can the Naked Mole-rat Teach Us About Cancer? [online] Cancer Research from Technology Networks. Available at: https://www.technologynetworks.com/cancer-research/articles/what-can-the-naked-mole-rat-teach-us-about-cancer-337173 [Accessed 14 Mar. 2021].
Hadi, F., Kulaberoglu, Y., Lazarus, K.A., Bach, K., Ugur, R., Beattie, P., Smith, E.S.J. and Khaled, W.T. (2020). Transformation of naked mole-rat cells. Nature, [online] 583(7814), pp.E1–E7. Available at: https://www.nature.com/articles/s41586-020-2410-x [Accessed 14 Mar. 2021].
University of Cambridge. (2020). Secrets of naked mole-rat cancer resistance unearthed. [online] Available at: https://www.cam.ac.uk/research/news/secrets-of-naked-mole-rat-cancer-resistance-unearthed#:~:text=Naked%20mole%2Drats%20can%20live,multiplying%2C%20according%20to%20new%20research. [Accessed 14 Mar. 2021].
Cassella, C. (2017). We Finally Know How Naked Mole Rats Survive Without Oxygen, And It’s Really Freaking Weird. [online] ScienceAlert. Available at: https://www.sciencealert.com/we-just-figured-out-how-naked-mole-rats-survive-low-oxygen-and-it-s-even-trippier-than-imagined#:~:text=Mice%20without%20oxygen%20die%20after,this%20type%20of%20suspended%20animation. [Accessed 14 Mar. 2021].
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