October 6, 2023

Not many people have heard of the naked mole rat. This 3-inch mammal is part of the rodent family and is primarily found underground in East Africa. Unlike their other rodent counterparts, they lack hair on their bodies making them look rather odd. And they live in large colonies that range from 70 up to 300 with all being birthed by a single female in the colony. While these features are both intriguing and unusual, it’s not these that scientists consider the most remarkable. Instead, it’s these creatures’ incredible anti-aging biochemical mechanisms that have attracted the most attention. With impressively low naked mole rat mortality rates, researchers have been trying to tap into their longevity secrets. And based on recent studies, they may have found an important clue.

As anti-aging biochemical mechanisms go, the naked mole rat has a decent amount.

The average lifespan of the naked mole rat is about 30 years, which is 10 times more than other rat species. In fact, many live in excess of 40 years. For some time, the reason for these low naked mole rat mortality rates was lacking. But recently, it has been discovered that these rodents produce high levels of a substance that slows aging and protects against disease. And now, scientists have found a way to transplant the gene responsible for these anti-aging biochemical mechanisms into other mice. The results of these experiments have been notable to say the least, extending rodent lifespan by several years. An as a result, the naked mole rat might similarly hold secrets to human anti-aging strategies as well.

“Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals.” – Vera Gorbunova, Professor of Biology and Medicine at University of Rochester, New York

Why the Naked Mole Rat?

Before discussing the latest anti-aging research, knowing a little about the naked mole rat is essential. Found in countries like Kenya and Ethiopia, these creatures don’t look like your typical rat. Instead, they are pink-skinned and nearly hairless except for some whiskers and hairs between their toes. Likewise, they are burrowing mammals, forming an intricate network of tunnels underground, rarely coming outside. Their primary source of food is that of plant tubers, which they eat underground as well. And as mentioned, only a single female births an entire colony with all others serving as diggers and workers. Come to think of it, they sound more like a colony of ants than one of mammals.

(Read up on the latest anti-aging innovations in this Bold story.)

While these characteristics make the naked mole rat unique, it’s other features that are more impressive. Not only are naked mole rat mortality rates low with their longevity lasting several decades. But likewise, these mammals don’t typically succumb to common diseases. Specifically, neurodegenerative conditions are rarely seen, and they are resistant to cardiovascular problems. Arthritis is also uncommon as are cancers among this species. It is these anti-disease and anti-aging biochemical mechanisms that interest researchers. And these qualities seem to be linked primarily to one chemical substance. It’s been finding and reproducing this substance that’s been the biggest challenge.

They may not look like much, but these little buggers have a handle on not growing old.

The Naked Mole Rat’s Longevity Gene

Currently, it appears low naked mole rat mortality rates are connected to a substance called high-molecular-weight hyaluronic acid (HMW-HA). This substance is known to markedly enhance a cell’s ability to repair itself from injury. It also offers significant protection to cells when it comes to cancers and malignancies. Compared to other rodent species, quantities of HMW-HA in naked mole rats are ten-fold greater. And it has been this discovery that led scientists to suspect this was the substance behind their anti-aging biochemical mechanisms. If similar levels of HMW-HA could be produced in humans, then longevity could be significantly increased. And we would have the naked mole rat to thank for it!

As yummy as it might sound, eating a naked mole rat isn’t going to accomplish this task. If higher HMW-HA levels are the target in humans, then it will have to be produced internally. Fortunately, the naked mole rat has a single gene sequence that’s responsible for making an enzyme called hyaluronan synthase 2. It is this enzyme that produces HMW-HA and might be transferrable to other mammals. Not only would these anti-aging biochemical mechanisms increase lifespan. But they would also reduce chronic disease burden in human populations. For some time, researchers have been trying to slow the degradation of HMW-HA in human beings. But combining these efforts with a longevity gene accounting for low naked mole rat mortality rates would be better.

“We hope that our findings will provide the first, but not the last, example of how longevity adaptations from a long-lived species can be adapted to benefit human longevity and health.” – Andrei Seluanov, Professor of Biology and Medicine, University of Rochester

The Latest HMW-HA Research

Naked mole rat mortality rates mean this rodent knows what’s up.

Recent research out of the University of Rochester has revealed that benefits of this longevity gene does exist. In an experiment involving mice, scientists used genetic engineering techniques to transplant the longevity gene that makes hyaluronan synthase 2. They took the gene from naked mole rats and modified them so they could be incorporated into regular mice. In doing so, they hoped to impart the same anti-aging biochemical mechanisms onto the mice. Since naked mole rat mortality rates are so low, this gene might reduce deaths of mice as well. As it turns out, they were right.

Extensive examinations of the mice receiving the naked mole rat longevity gene were performed. In terms of longevity itself, the mice receiving the gene lived 4.4% longer than expected. But these weren’t the only improvements. These same mice also had reduced occurrence of tumors and skin cancers. They also were found to have lower levels of inflammation throughout their bodies. And the mice also had a healthier gut and a higher level of overall health. Based on these findings, the researchers believed the study substantiated the anti-aging biochemical mechanisms linked to HMW-HA. It would seem this substance is a big reason why naked mole rat mortality rates are so low.

Burrowing Toward Greater Longevity

The most remarkable thing about this research is how certain species of mammals have adapted differently than others. The low naked mole rate mortality rates and extended longevity are due to its unique longevity gene. By producing much higher levels of HMW-HA, these animals live longer and healthier. Leveraging this knowledge and expanding precision medicine techniques, humans might be able to do the same. The more we learn about the various anti-aging biochemical mechanisms of other creatures, the more insight we will have.

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(Editor’s note: Welcome to Bold’s series on the Nobel Prize, its winners, and their contributions. Read up on the notable winners in physics here.)

A Nobel Prize in Physiology or Medicine means a direct benefit to the health of mankind.

Like other Nobel Prizes in various fields, the Nobel Prize in Physiology or Medicine was first awarded in 1901. Since that time, there has been a total of 114 prizes given to a total of 226 different Nobel Laureates. Each year, professors at the Karolinska Institute convene to determine potential nominees. Subsequently, at least since 1977, a select committee of five professors then assess their merit. In doing so, it is evident that physiologists and scientists in the basic sciences receive preference over those in applied science. Their perspective thus appears to be that Nobel Prizes that changed medicine at a more basic level deserve the most credit.

Among the recipients of the Nobel Prize in Physiology or Medicine, nearly everyone deserves recognition. Discoveries range from those that revolutionized the care of infectious diseases to those involving genetic therapies. In addition, the award has not been without its fair share of controversy at times. In 1949, Antonio Moniz received the award for work with prefrontal lobotomies. This was highly protested by the medical community on an ethical basis. Likewise, in 1952, litigation occurred after one scientist was not included as a recipient. Ultimately, court rulings awarded this individual patent rights alongside the Nobel Prize winner. Regardless, the following offers a collection of Nobel Prizes that changed medicine and the incredible intellects behind them.

Emil Adolf von Behring – Nobel Prize in Physiology or Medicine 1901

At the turn of the 20^th century, little was known about the human immune system. But Emil Adolf von Behring was able to demonstrate that our immune system produced specific immune substances. He showed that serum from a horse could be transferred to a human to provide immunity against a disease. His work then used this strategy to cure and prevent infections from diphtheria. This completely changed approaches to infectious diseases thereafter and build a strong foundation for the study of immunology. It is therefore included on the list of critical Nobel Prizes that changed medicine.

Frederick Banting and John Macleod – Nobel Prize in Physiology or Medicine 1923

Around this time, there was a general belief that diabetes resulted from a lack of insulin as a result of pancreatic deficiency. If insulin could be isolated and provided to diabetics, then effective treatments might result. To this end, Frederick Banting believed a substance called trypsin metabolized insulin. So, he along with John Macleod treated dogs to eliminate trypsin, which allowed them to harvest insulin to treat diabetes. Thus, this is one of the Nobel Prizes that changed medicine and the lives of millions with diabetes thereafter.

You know you’ve accomplished something great for the world when you win a Nobel Prize in Medicine.

Sir Alexander Fleming, Ernst Chain and Sir Howard Walter Florey – Nobel Prize in Physiology or Medicine 1945

It’s easy to appreciate that the discovery of penicillin deserves recognition. This is why it is included among the most notable Nobel Prizes that changed medicine. Sir Alexander Fleming was the scientist who initially discovered the substance when noticing bacterial growth was impeded by a mold. Once isolated, however, penicillin proved to be rather unstable. It was thus the work of Ernst Chain and Howard Florey that allowed the pharmaceutical production of penicillin for widespread use. Naturally, this ushered in the era of antibiotic care.

Francis Crick, James Watson and Maurice Wilkins – Nobel Prize in Physiology or Medicine 1962

The award giving to those defining the structure of DNA is certainly among the most important Nobel Prizes that changed medicine. Maurice Wilkins initiated these discoveries with his work with x-ray crystallography. Watson and Crick then used Wilkins’ images to define the double helix structure of DNA and its protein bases. Not only did this explain how DNA could be utilized as a code but also offered insight about its replication. Today’s fields of genetics and genomics would not exist without these critical findings. (Read up on a recent genetics breakthrough in this Bold story.)

Allan M. Cormack and Godfrey N. Hounsfield – Nobel Prize in Physiology or Medicine 1979

For decades, x-rays had been used in medicine for diagnostic purposes. But with the introduction of computing in the 1950s, new possibilities emerged. These advanced technologies were thought to have potential applications in medicine, particularly in imaging diagnostics. Cormack and Hounsfield believed by sending x-rays at different angles, cross-sectional images of the body’s structures could be attained. Hounsfield developed the apparatus while Cormack determined the complex computer calculations. The result was computerized tomography, or the CT scan. Given the subsequent impact on diagnostics of this discovery, it too is included among the Nobel Prizes that changed medicine.

The Nobel Prizes that changed medicine are the ones with irrefutable benefit to mankind.

Stanley B. Prusiner – Nobel Prize in Physiology or Medicine 1997

While bacteria and viruses were known to be infectious particles, proteins alone were not. Yet, certain degenerative diseases affecting humans and animals appeared to have an infectious cause. Prusiner is the recipient of one of the Nobel Prizes that changed medicine because his work identified these infectious proteins. Prusiner labelled these proteins “prions” and demonstrated that they had abnormally folded structures. These folded structures, which resulted in cellular dysfunction, could be transferred from one cell to another. His findings were important because it defined a completely new infectious material. This has since led to a number of diseases being called prion disease.

Barry J. Marshall and J. Robin Warren – Nobel Prize in Physiology or Medicine 2005

One of the criteria for Nobel Prizes that changed medicine is the capacity to cause paradigm shifts in care. This was certainly relevant to the work performed by Barry Marshall and Robin Warren. At the time of their work, gastric ulcers were considered chronic illnesses and the result of excess acid production. But Warren discovered clumps of bacteria within gastric ulcer sites that had never been seen. Marshall was then able to define these bacteria, now called Helicobacter pylori, which had not previously been isolated. They were then able to show that only by eradicating these bacteria with antibiotics could gastric ulcer patients be cured. Notably, their findings completely changed how gastric ulcer is treated, and it has provided cures to many in the process.

What is the Broadband Equity Access Deployment (BEADs) Program? Find out in this Bold explainer!

Day: October 6, 2023

Notable Nobel Prize Winners in Medicine

Emil Adolf von Behring – Nobel Prize in Physiology or Medicine 1901

Frederick Banting and John Macleod – Nobel Prize in Physiology or Medicine 1923

Sir Alexander Fleming, Ernst Chain and Sir Howard Walter Florey – Nobel Prize in Physiology or Medicine 1945

Francis Crick, James Watson and Maurice Wilkins – Nobel Prize in Physiology or Medicine 1962

Allan M. Cormack and Godfrey N. Hounsfield – Nobel Prize in Physiology or Medicine 1979

Stanley B. Prusiner – Nobel Prize in Physiology or Medicine 1997

Barry J. Marshall and J. Robin Warren – Nobel Prize in Physiology or Medicine 2005

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Why the Naked Mole Rat?

The Naked Mole Rat’s Longevity Gene

The Latest HMW-HA Research

Burrowing Toward Greater Longevity

Emil Adolf von Behring – Nobel Prize in Physiology or Medicine 1901

Frederick Banting and John Macleod – Nobel Prize in Physiology or Medicine 1923

Sir Alexander Fleming, Ernst Chain and Sir Howard Walter Florey – Nobel Prize in Physiology or Medicine 1945

Francis Crick, James Watson and Maurice Wilkins – Nobel Prize in Physiology or Medicine 1962

Allan M. Cormack and Godfrey N. Hounsfield – Nobel Prize in Physiology or Medicine 1979

Stanley B. Prusiner – Nobel Prize in Physiology or Medicine 1997

Barry J. Marshall and J. Robin Warren – Nobel Prize in Physiology or Medicine 2005

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Connect

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