The naked mole rat is not a very remarkable animal, but its ecology makes it one of the most fascinating animals for aging research. These small, wrinkled rodents can live for decades, rarely develop cancer, and appear to be unusually protected from many diseases that normally come with age.
Researchers at the University of Rochester have shown that one of these biological benefits can be transferred to another mammal. By introducing a gene associated with naked mole rats’ unusually high levels of high molecular weight hyaluronic acid (HMW-HA), the researchers improved the mice’s health and slightly extended their lifespans.
The works published in nature (2023) suggested that at least some longevity traits evolved in long-lived animals may be adaptive beyond the species that developed them. Genetically modified mice lived healthier lives and had an average lifespan of about 4.4 percent longer than normal mice.
“Our study provides proof of principle that unique longevity mechanisms evolved in long-lived mammalian species can be applied to extend lifespans in other mammals,” says Vera Gorbunova, Doris Johns Cherry Professor of Biology and Medicine at the University of Rochester.
Gorbunova, along with biology professor Andrei Seruanov and colleagues, focused on the genes that help produce HMW-HA. This substance is abundant in naked mole rats and has been linked to remarkable resistance to cancer, inflammation, and age-related decline.
Why naked mole rats fascinate older scientists
Naked mole rats are about the same size as mice, but their lifespans are unusually long for a rodent. They can live up to 41 years, which is almost 10 times more than similarly sized rodents.
Their longevity is not the only reason scientists study them. As naked mole rats age, they appear to avoid many conditions common to other mammals, including neurodegeneration, cardiovascular disease, arthritis, and cancer. For decades, Gorbunova, Seruanov, and other researchers have studied how these animals maintain their resilience.
One of the big clues is HMW-HA. Naked mole rats carry about 10 times more of it than mice or humans. In a previous study, researchers found that removing HMW-HA from naked mole rat cells increased the likelihood of those cells forming tumors.
This discovery raises powerful questions. If HMW-HA helps naked mole rats resist cancer and age-related damage, could the same mechanism work in other animals?
Transplantation of longevity genes in naked mole rats
To test this idea, the Rochester team engineered mice to carry a naked mole rat version of the hyaluronan synthase 2 gene. This gene helps produce the protein that produces HMW-HA.
All mammals have a version of hyaluronan synthase 2, but the naked mole rat’s version appears to be particularly active. It seems to promote stronger gene expression and lead to more production of protective molecules.
The engineered mice developed higher levels of hyaluronic acid in some tissues. It also showed strong protective effects against naturally occurring tumors and chemically induced skin cancer.
Its effects were not limited to resistance to cancer. Mice carrying the naked mole rat gene remained healthier overall, lived longer than normal mice, had less age-related inflammation in multiple tissues, and maintained better intestinal health.
Reducing inflammation was particularly important because chronic inflammation is one of the key biological hallmarks of aging. Researchers believe that HMW-HA may work in part by directly affecting the immune system, but further research is needed to explain exactly how HMW-HA produces such widespread benefits.
A small increase in lifespan has big implications.
The increase in life expectancy was approximately 4.4%, which was modest. But more importantly, the longevity mechanisms of one mammal were successfully transferred to another.
So this discovery is more than just a mouse study of a single gene. This supports the idea that long-lived species in nature may contain biological tools that can be used to study, adapt, and perhaps improve the health of other animals.
“It took 10 years after we discovered HMW-HA in naked mole rats to show that HMW-HA improves the health of mice,” Professor Gorbunova says. “Our next goal is to transfer this benefit to humans.”
Researchers believe there may be two main ways to achieve that goal. One is to slow down the breakdown of HMW-HA in the body. The other is to increase production.
“We have already identified molecules that slow the breakdown of hyaluronic acid and are testing them in preclinical studies,” Seruanov says. “We hope our findings provide the first, but not the last, example of how longevity adaptations from long-lived species can benefit human longevity and health.”
New research adds to the naked mole rat story
From 2023 onwards nature Research continues to provide new clues as to why naked mole rats age differently than other mammals. Survey in 2025 science reported another potential longevity mechanism involving cGAS, a protein well known for its role in immune defense. In humans and mice, cGAS can interfere with some types of DNA repair, but the naked mole rat version appears to help cells repair DNA damage more effectively. The study found that specific changes in proteins in naked mole rats improve genome stability and delay signs of aging in an experimental model.
This new study does not replace the discovery of HMW-HA. rather, it reinforces broader patterns. Naked mole rats’ unusually long and healthy lives are likely due to several overlapping defenses, including cancer resistance, inflammation control, DNA repair, and tissue protection.
It is important for human aging research. It is unlikely that a single molecule will be a simple fountain of youth. But each discovery gives scientists new possibilities to target the biological processes that cause age-related diseases.
Gene transfer research in 2023 remains an amazing proof of concept. A survival strategy evolved in one of nature’s strangest mammals has helped mice resist disease, age more smoothly, and live longer. The next challenge is to determine whether the same biological tricks can be safely adapted to extend human healthspans.
