UP experts contribute to discovery of new ‘superpowers’ in mole rats, which could inform human health interventions

University of Pretoria (UP) scientists have contributed to discovering how the naked mole rat is able to withstand heart attacks and fend off bowel cancer, two of the most fatal human ailments in the developed world. Their findings were published recently in two Nature Communications papers.

Prof Nigel Bennett and Dr Daniel Hart, co-authors on both papers and experts in mole rat evolution at UP’s Department of Zoology and Entomology, say the findings add to a long list of mole rat “superpowers” that have already been discovered, including slower ageing, natural contraception and the ability to bypass pain responses – all of which are of great interest to biomedical researchers working on human health.

“The main reason we believe mole rat have these ‘superpowers’ is because they live in such harsh environments underground,” Dr Hart says, adding that there is very little oxygen underground and that the roots mole rats eat are tough, fibrous and even toxic to most mammals.

He says the best place to study colon cancer in mammals, a disease characterised by cell division gone wrong, is in the intestinal crypt, a small pocket at the base of the intestine where stem cells are found. These cells normally begin to divide, and specialise into intestinal cells that line and protect the gut.

“If something is wrong with the stem cells, the animal has big problems,” Dr Hart says. Mice, for instance, will die when given a cancer-causing agent that targets those stem cells.

But not the naked mole rat.

“We saw no physical damage in the animal when we attempted to induce the precursor to colon cancer, and no signs of distress – just business as usual,” Dr Hart explains. When they had a closer look at the intestinal crypt using specialised scanning techniques, they found that the stem cells had simply stopped dividing to protect themselves against damage from the cancer-causing chemical.

“It’s like [the stem cells] batten down the hatches until the storm is gone; it’s as if they go into a dormant stage,” Dr Hart says. “Then when the stressor has left, they come out and start dividing again.”

The researchers also found more intestinal adult stem cells, and more cells that protect against gut cancers and degradation due to ageing. This is not surprising, Dr Hart says, because scientists have already noticed that all mole rat species have a very low incidence of cancer, so it’s likely these kinds of mechanisms confer protection against all cancers, not just colon cancer.

Much of the experimentation behind the cancer discovery was done at UP at the specialised mole rat laboratory established by Prof Bennett. Dr Hart says the work would have been impossible without their collaborators from the University of Oxford in the UK, led by Dr Shazia Irshad and Dr Shamir Montazid, as well as Dr Sheila Bandyopadhyay of Rutgers University in the US.

The UP lab, which was recently featured in the “Dark” episode of the BBC documentary series Mammals, is home to about eight different mole rat species, many of which are unique to South Africa and exclusively studied there. International researchers working on more common global species like the naked mole rat often look to UP for evolutionary comparisons and cross-species studies.

“We have opportunities to work with some of the best scientists and laboratories in the world because we have these mole rats,” Dr Hart says. “We aren’t just seen as a source of material or source of potential, but as equal collaborators.”

To bring the bowel cancer finding closer to human biomedical research, the genetic markers must be pinpointed next, Dr Hart explains, so that gene therapies for equivalent human genes can be investigated. This is exactly what the international team of scientists studying naked mole rat heart attacks have done: they mapped the genetic adaptations that keep a naked mole rat’s heart beating despite it being deprived of oxygen and nutrients.

In humans and other mammals, a heart attack occurs when the heart’s oxygen and food supply is interrupted, due to a blockage in blood vessels, for instance. When researchers tried to induce a heart attack in the naked mole rat, as they would usually do when studying mice and other mammals, the super critter’s little heart just kept beating and suffered almost no damage. The research team went on to pinpoint the specific metabolic and genetic adaptations that protect the naked mole rat’s heart.

Prof Bennett’s laboratory helped conceive this study and provided species comparisons for this experiment; his team praised the brilliance of the international team, led by Dr Dunja Aksentijevic and Dr Chris Faulkes of Queen Mary University of London, for the heart findings.

Click on the infographic in the sidebar to learn about the seven superpowers of the African mole rat.

Dr Daniel Hart and Prof Nigel Bennett

June 4, 2024

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Researchers
  • 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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  • Dr Daniel Hart
    Dr Daniel Hart is a postdoctoral fellow at the University of Pretoria. His research focuses on the evolutionary physiological and biomedical studies of African vertebrates.

    Dr Daniel Hart was part of an international team with Prof Nigel Bennett whose research into African mole-rats was not only published in the distinguished journal Science but made the cover.

    Prof Nigel Bennett, a professor in UP’s Department of Zoology and Entomology, and post-doctoral fellow Dr Daniel Hart worked closely with the Max Delbrück Center for Molecular Medicine in Berlin, Germany on their recent research, the findings of which show that mole-rats communicate in their own dialect.

    He tells us more about their groundbreaking research.

    What makes African mole-rats so interesting?
    DH: They are great models to show how animals adapt to their environment. For example, their broad spectrum of sociality has been brought about by the different species inhabiting different climatic regions. Simultaneously, their incredible ability to withstand hypoxic (low oxygen) conditions has come about because of their exclusive subterranean lifestyle.

    What made you focus your research on them?
    DH: When I began my research career, a wise mentor gave me a piece of advice: study animals that you can ask interesting questions about. So far, I have not found an animal that you can ask more interesting questions about than African mole-rats ­­– the number of exciting questions and answers that mole-rats have to offer drew me to studying them.

    How does their social and communication habits have an impact on how we understand them?

    DH: Naked mole-rats live in large families (50 to 60 individuals), with some colonies reaching 300, controlled by one female, the queen. Each colony member has its own “job”, and everyone recognises their own colony and family members, even in the dark. Even after the vast number of studies on these amazing animals, how the colony structure is maintained has somewhat eluded us. But, like humans, it may come down to dialects to some extent. From this study, we have learnt that each mole-rat colony has its own dialect, dictated by the queen, allowing colony cohesion and detection of intruders. Interestingly, this dialect can be learnt, which is an uncommon ability in most animals. This new understanding brings us closer to figuring out how these large families work together and stay together. This understanding can possibly help us in furthering our knowledge about human dialects.

    Are there any other animals that provide as interesting an array of applications as the mole-rat?

    DH: We are fortunate, as Africa has a treasure trove of unique animals with remarkable features and abilities. One such animal we are working on is the tenrec, which is a fantastic model of a prehistoric mammal. With these animals, we hope to peer back in time to unravel essential questions about evolution. Like the mole-rats, they also possess remarkable physiological and molecular traits, which could be vital to biomedical studies.

    What do you do in your spare time?
    DH: I have quite a big interest in other scientific subjects, namely astrophysics, astronomy and cosmology. I also enjoy listening to books or podcasts on these subjects and reading articles when I get a chance. Also, I am passionate about sport, so I enjoy catching up on the world’s sporting events when I can.
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