Naked mole rats may not look particularly handsome, but their biology has made them one of the most fascinating animals in aging research. These small, wrinkled rodents can live for decades, rarely develop cancer and appear to be unusually well protected from many diseases normally associated with old age. Researchers at the University of Rochester have shown that one of these biological advantages can be transferred to another mammal. By transferring a gene associated with the unusually high levels of high molecular weight hyaluronic acid (HMW-HA) in naked mole rats, the team improved the health of mice and slightly extended their lifespan. The study, published in Nature in 2023, suggested that at least some of the longevity traits that have evolved in long-lived animals may be transferable to other species. The genetically modified mice lived healthier and had a mean life expectancy that was around 4.4 percent longer than that of ordinary mice.
Why Naked Mole Rats Fascinate Scientists in the Field of Ageing
“Our study provides proof of principle that unique longevity mechanisms that have evolved in long-lived mammalian species can be transferred to improve the lifespan of other mammals,” said Vera Gorbunova, Doris Johns Cherry Professor of Biology and Medicine at Rochester. Gorbunova, along with Andrei Seluanov, a professor of biology, and her colleagues focused on a gene that helps in the production of HMW-HA. This substance is abundant in naked mole rats and has been linked to their remarkable resistance to cancer, inflammation and age-related decline.
Naked mole rats are about the same size as mice, but their life expectancy is exceptionally long for rodents. They can live up to 41 years, almost ten times longer than rodents of a similar size. Their long life is not the only reason why scientists are studying them. As they age, naked mole rats appear to avoid many diseases that commonly affect other mammals, including neurodegeneration, cardiovascular disease, arthritis and cancer. For decades, Gorbunova, Seluanov and other researchers have been studying how these animals remain so resilient.
One important clue is HMW-HA. Naked mole rats carry about ten times more of it than mice and humans. In previous work, the researchers found that the cells of naked mole rats were more likely to form tumors when HMW-HA was removed from them. This finding raised an important question: If HMW-HA helps naked mole rats resist cancer and age-related damage, could the same mechanism work in another animal?
Transfer of a Longevity Gene from Naked Mole Rats
The researchers specifically transferred the hyaluronan synthase 2 gene (HAS2) from the genome of naked mole rats to mice in order to test whether the exceptionally high content of high molecular weight hyaluronic acid (HMW-HA) could also be replicated in another mammal. This gene controls the production of an enzyme that is responsible for the formation of hyaluronic acid – a structural molecule that is not only found in the skin and connective tissue, but also plays an important role in cell protection, inflammation regulation and tissue renewal. In the genetically modified mice, the increased activity of this gene led to significantly higher levels of hyaluronic acid in several organs. This apparently enabled the cells to be better protected against stress, DNA damage and degenerative growth processes, which was reflected in a lower tumor incidence, among other things.
However, the effect was not limited to cancer resistance, but also affected several classic characteristics of ageing. The mice with the naked mole rat gene showed better overall physical fitness in old age, fewer chronic inflammatory processes in tissues such as the liver and intestine and a more stable intestinal barrier, which is considered important for immune balance and metabolism. As chronic, low-grade inflammation (“inflammaging”) is considered to be a central driver of the ageing process, this reduction is of particular biological significance. In addition, the researchers observed improved tissue integrity and slower age-related degeneration of various organ systems. On average, the lifespan of the animals increased moderately but measurably, which indicates that individual evolutionary protective mechanisms of long-lived species could in principle also be transferable to other mammals. However, the researchers emphasize that it is not yet fully understood how exactly HMW-HA interferes with complex signaling pathways of the immune system and cell aging and what long-term effects such a genetic modification would have.
A Small Gain in Lifespan With Major Consequences
The extension of the average lifespan by around 4.4 % seems rather small at first, but it is certainly relevant in ageing research in complex mammals because even small effects often point to fundamental biological processes. What is more decisive in this study than the pure lifespan, however, is that for the first time a complete longevity mechanism from the exceptionally long-lived naked mole rat could be functionally transferred to another mammal.
The work thus shows that it is not just the effect of a single gene, but a biological protection system that influences several processes simultaneously – such as inflammation, tissue stability and tumor development. It is precisely this combination that is typical of long-lived species that have developed mechanisms over the course of evolution to better control cell damage and age-related diseases. The results therefore support the overarching idea that such evolutionary “tools of longevity” need not be unique to a species. Instead, they could in principle be isolated, understood and possibly adapted to provide health benefits in other organisms – perhaps even in humans in the future.
The researchers led by Vera Gorbunova are working on transferring a longevity mechanism from naked mole rats to humans. The focus is on the greatly increased amount of high molecular weight hyaluronic acid (HMW-HA), which protects tissue in these animals, reduces inflammation and apparently also inhibits cancer processes. After around ten years of research, they were able to show that this mechanism also has health benefits in mice. For a possible application in humans, they are pursuing two approaches: either slowing down the degradation of hyaluronic acid or specifically increasing its production. The first active ingredients that inhibit degradation are already being tested in preclinical studies. The basic idea is to harness such naturally occurring protective mechanisms from long-lived animal species for human health and possibly also to slow down the ageing process.
More Recent Research Results Supplement the Findings on Naked Mole Rats
Since the 2023 Nature study, naked mole rats continue to provide new clues as to why they age so differently from other mammals. A 2025 study in Science reported another potential longevity mechanism involving cGAS, a protein better known for its role in immune defense. In humans and mice, cGAS can interfere with certain forms of DNA repair, but the naked mole rat version appears to help cells repair DNA damage more effectively. This study found that specific changes in the naked mole rat protein improved genome stability and delayed signs of aging in experimental models.
This recent work does not replace the HMW-HA finding. Instead, it underpins a broader pattern. Naked mole rats likely owe their unusually long, healthy lives to several overlapping defense mechanisms, including cancer resistance, inflammation control, DNA repair and tissue protection. This is important for research into human ageing. It is unlikely that a single molecule will become a simple fountain of youth. But each discovery opens up another possible avenue for scientists to tackle the biological processes that drive age-related diseases. The 2023 gene transfer study remains an impressive proof of concept. A survival strategy that evolved in one of nature’s strangest mammals helped mice resist disease, age more gently and live longer. The next challenge is to determine whether the same biological tricks can be safely adapted to improve the health span of humans.