Naked mole rats are not much to look at, 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 seem unusually protected from many of the diseases that normally arrive with age.

Researchers at the University of Rochester showed that one of those biological advantages can be moved into another mammal. By transferring a gene linked to the naked mole rat's unusually high levels of high molecular weight hyaluronic acid (HMW-HA), the team improved health and modestly extended lifespan in mice.

The work, published in Nature in 2023, suggested that at least some longevity traits that evolved in long-lived animals may be adaptable beyond the species that developed them. The genetically modified mice lived healthier lives and had an approximate 4.4 percent increase in median lifespan compared with ordinary mice.

"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," says Vera Gorbunova, the Doris Johns Cherry Professor of biology and medicine at Rochester.

Gorbunova, along with Andrei Seluanov, a professor of biology, and their colleagues, focused on a gene that helps produce HMW-HA. This substance is abundant in naked mole rats and has been tied to their striking resistance to cancer, inflammation, and age-related decline.

Why Naked Mole Rats Fascinate Aging Scientists

Naked mole rats are about the size of mice, yet their lifespans are extraordinary for rodents. They can live up to 41 years, nearly ten times longer than similarly sized rodents.

Their long lives are not the only reason scientists study them. As they age, naked mole rats appear to avoid many conditions that commonly affect other mammals, including neurodegeneration, cardiovascular disease, arthritis, and cancer. For decades, Gorbunova, Seluanov, and other researchers have been investigating how these animals stay so resilient.

One major clue is HMW-HA. Naked mole rats carry roughly ten times more of it than mice and humans. In earlier work, researchers found that when HMW-HA was removed from naked mole rat cells, those cells became more likely to form tumors.

That finding raised a powerful question. If HMW-HA helps naked mole rats resist cancer and age-related damage, could the same mechanism work in a different animal?

Transferring a Naked Mole Rat Longevity Gene

To test the idea, the Rochester team engineered mice to carry the naked mole rat version of the hyaluronan synthase 2 gene. This gene helps make the protein that produces HMW-HA.

All mammals have a version of hyaluronan synthase 2, but the naked mole rat version appears to be especially active. It seems to drive stronger gene expression, leading to greater production of the protective molecule.

The modified mice developed higher levels of hyaluronan in several tissues. They also showed stronger protection against spontaneous tumors and chemically induced skin cancer.

The effects were not limited to cancer resistance. The mice carrying the naked mole rat gene stayed healthier overall, lived longer than regular mice, had less inflammation in multiple tissues as they aged, and maintained better gut health.

Because chronic inflammation is one of the major biological features of aging, the reduction in inflammation was especially important. The researchers believe HMW-HA may work partly by directly influencing the immune system, although more research is needed to explain exactly how it produces such broad benefits.

A Small Lifespan Gain With Big Implications

The increase in median lifespan was about 4.4 percent, which is modest. But the larger significance is that a longevity mechanism from one mammal was successfully transferred to another.

That makes the finding more than a mouse study about a single gene. It supports the idea that nature's long-lived species may contain biological tools that can be studied, adapted, and possibly used to improve health in other animals.

"It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice," Gorbunova says. "Our next goal is to transfer this benefit to humans."

The researchers believe there may be two main ways to pursue that goal. One would be to slow the breakdown of HMW-HA in the body. Another would be to increase its production.

 Source: ScienceDaily