Death is temporary - the resurrection of the naked mole rat

Imagine putting 100 mice in a shoebox, taping the box shut and burying it a metre underground. The result should be obvious – 100 dead mice. In fact, if any animal is deprived of oxygen for too long the result is fatal – any animal except one, that is.

When the naked mole-rat is completely deprived of oxygen, it stops breathing, its heart rate drops and it subsequently dies. However, its death is temporary and if within a certain time it is given oxygen again, it comes back to life.

While it is incredible that these tiny mammals from East Africa can survive chronic oxygen deprivation in the underground environments in which they live, the fact that they are able to bring themselves back to life is almost unbelievable.

*Prof Nigel Bennett and Dr Heike Lutermann, of the University of Pretoria's Department of Zoology and Entomology, are involved in an exciting study on this topic that has been featured in Science. Visiting researcher and another lead investigator in the study, Prof Thom Park of the University of Illinois in the USA, says: 'This was a challenge so big that it took three labs on three continents to solve it.' Prof Gary Lewin of the Max Delbrück Centre for Molecular Medicine at the University of Berlin, Germany, was the other lead investigator in the study.

While this discovery is going to necessitate rewriting the world's zoological textbooks, it also brings exciting prospects to the realm of human health. Understanding how one mammal is able to survive without oxygen could lead to human lives being saved in times of crisis, such as when someone is in a car accident or suffers a stroke or a heart attack.

While naked mole-rats are adapted to the high levels of carbon dioxide in their underground clay castles, this study observed the results when mole rats had no access to oxygen at all. During these periods, the naked mole-rat reduces its heart rate to the extent that it almost appears to have stopped. It keeps it pumping just enough to circulate blood. The scientists are not yet fully certain how these animals manage to reduce their heart rate to such an extent.

Oxygen deprivation is inevitable when more than 70 naked mole-rats live together underground in an area not much bigger than a rugby ball. Prof Park explains that generally oxygen does not diffuse very well through soil, particularly the clay soil in which naked mole-rats live. With so many individuals living in a confined space, oxygen is very quickly depleted and far too much carbon dioxide is produced. Describing the environment as hostile, Prof Bennett adds that the humidity in these conditions is nearly 100%. Roots of plants also produce carbon dioxide. Yet naked mole rats survive these hypoxic conditions without any long-term damage.

Through this international collaboration, the researchers discovered that when the naked mole-rat is deprived of oxygen, it uses internal pathways to survive that no other mammal uses. It alters its metabolic systems to function more like a plant than an animal, releasing fructose into the blood, which is then taken to the brain. Its brain contains cells that can utilise fructose, enabling cellular functions to continue. Aerobic energy production stops and the animal operates on anaerobic systems, relying on fructose for energy instead of glucose. Once oxygen is restored, they switch back to their usual pathways.

If scientists can understand the biochemistry of the naked mole-rat and unlock the mechanisms that switch the pathways during oxygen deprivation, increasing and activating the number of brain cells that are able to utilise fructose, they might be able to apply this knowledge to humans, improving our chance of survival in extreme situations.

The naked mole-rat is fascinating and defies most characteristics of a mammal. These hardy little animals have been recorded to live for over 30 years and studies suggest they are immune to cancer. They are also the only cold-blooded mammal. Their social structures give scientists much to grapple with, resembling social insects like bees rather than mammals.

These researchers are now planning to conduct a comparative study between social and solitary species to find out if these traits are common to all subterranean mole-rats.

In a world where trees are being chopped down to make space for development and with ever-increasing levels of carbon dioxide in the atmosphere, we may all soon be living in a hypoxic environment. Naked mole-rats might very well be the key to our survival.

Prof Bennett concludes: 'If this tiny animal is able to live for over 30 years with very little oxygen, imagine if we understood these pathways and applied them to humans…'

* Prof Nigel Bennett holds the Austin Roberts Chair of African Mammalogy and the SARChI Chair of Mammalian Behavioural Ecology and Physiology.

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Researchers

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  Professor Nigel Bennett

  Professor Nigel Bennett has been at the University of Pretoria (UP) for 26 years. He holds a BSc (Hons) in Zoology, which he obtained at Bristol University in the UK, and undertook his PhD studies at the University of Cape Town.
  
  His research focus is animal physiology and behaviour using the African mole rat as his model animal. His work is directed primarily at studying the social regulation of reproduction in mole rats.
  
  Prof Bennett’s research record ranks him among the best researchers studying social regulation of reproduction in any group of mammals in the world. He has investigated cooperative breeding in mammals from a variety of perspectives. This multi-faceted approach has led to an integrated understanding of reproductive suppression in mole rats of a type that has not been achieved for any other taxa. His research has set the benchmark for our understanding of phylogenetic and ecological constraints that regulate reproductive success and social evolution in mammalian species.
  Prof Bennett has always been interested in why some organisms adopt a social lifestyle and others do not. As a young boy, he was fascinated by how wood ants worked for the common good of a queen. His interest in mole rats came about while he was an undergraduate at Bristol University, after he had read a seminal paper by scientist Jennifer Jarvis on cooperative breeding in the naked mole rat. Upon obtaining a position as a doctoral candidate, Prof Bennett wanted to see if this was a feature common to other African mole rats. He went on to study the Damaraland mole rat, and found it to have incredible social organisation similar to that of social insects and termites.
  
  Prof Bennett is now the world leader in African mole rat biology, particularly in reproductive physiology. A research milestone for him was discovering that breeding female naked mole rats orchestrate non-breeding males and females in the colony to exhibit high prolactin levels. This inhibits the release of hormones that stimulate the development of reproductive activities in the gonads, as evidenced by a lack of follicular development in ovaries and a reduction in numbers and motile sperm in testes. Prolactin also results in individuals exhibiting helping behaviour and cooperative care of the young.
  
  After nearly three decades of research on the reproduction of social African mole rats, Prof Bennett has not been able to determine how the breeding female actually inhibits reproduction in physiologically suppressed animals. This would be the magic bullet for potential contraception in humans.
  He leads a research group that strives to unravel how social evolution arose in African mole rats – solving this puzzle has important implications as to how social evolution arose among hominids. Essentially, it comes down to food acquisition and protection from predators, which is a central theme in social evolution in most mammalian groups.
  
  Two people influenced his career: Prof Brian Follett – who supervised Prof Bennett’s honours project and whose infectious enthusiasm for science and incredible lectures fired up Prof Bennett’s imagination – and Prof Jennifer Jarvis, who drove his passion to work on mole rats.
  
  In 2021, Prof Bennett was made an honorary member of the American Society of Mammalogists, a title bestowed on fewer than 100 luminaries in a century. He has been a visiting professor at the School of Chemical and Biological Sciences at the University of London’s Queen Mary College since 2005. More recently, he was a visiting professor at the Department of Zoology at King Saud University in Saudi Arabia.
  
  He is a member of the Academy of Science of South Africa, and a fellow of the Zoological Society of London, the Royal Society of South Africa and the African Academy of Sciences.
  
  Prof Bennett was awarded the UP Chancellor’s Medal for his research on three occasions and has received the Exceptional Academic Achiever Award for the past 14 years. He was also the recipient of the Zoological Society of Southern Africa’s gold medal and received the Havenga Prize for outstanding contributions to Life Sciences, awarded by the Academy of Science and Arts of South Africa. UP awarded him the University of Pretoria Commemorative Research Medal for being one of the top 100 scientists in 100 years of its existence.
  
  Prof Bennett has served as president of the Zoological Community of Southern Africa for two years. He is also editor-in-chief of the Journal of Zoology and a past editor of Proceedings of the Royal Society B: Biological Sciences. In 2013, he was the handling editor of Biology Letters, another Royal Society of London journal. He has published 433 papers in international peer-reviewed scientific journals, co-authored a specialist book published by Cambridge University Press and has penned 15 chapters in books.
  
  In his spare time, Prof Bennett travels to different countries in Africa to explore the wildlife. He particularly enjoys visiting the mountain gorillas in Rwanda and Uganda, and the eastern lowland gorillas of the Democratic Republic of the Congo. He is also an avid collector of African art and frequently visits markets to add to his collection.
  
  If he were not a researcher, Prof Bennett would have liked to have been a game warden in one of East Africa’s national parks to contribute to the protection of the incredible African fauna from poaching.
  
  ORCID ID: 0000-0001-9748-2947
  

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  Death is temporary - the resurrection of the naked mole rat