In a groundbreaking endeavor, researchers on the University of Rochester have successfully transferred a long life gene from naked mole rats to mice, leading to improved health and an extension of the mouse’s lifespan.

Naked mole rats, known for his or her long lifespans and exceptional resistance to age-related diseases, have long captured the eye of the scientific community. By introducing a particular gene liable for enhanced cellular repair and protection into mice, the Rochester researchers have opened exciting possibilities for unlocking the secrets of aging and increasing human lifespan.

Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species may be exported to enhance the lifespans of other mammals.”

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

Gorbunova, together with Andrei Seluanov, a professor of biology, and their colleagues, report in a study published in Nature that they successfully transferred a gene liable for making high molecular weight hyaluronic acid (HMW-HA) from a unadorned mole rat to mice. This led to improved health and an approximate 4.4 percent increase in median lifespan for the mice.

A singular mechanism for cancer resistance

Naked mole rats are mouse-sized rodents which have exceptional longevity for rodents of their size; they’ll live as much as 41 years, nearly ten times so long as similar-size rodents. Unlike many other species, naked mole rats do hardly ever contract diseases-;including neurodegeneration, heart problems, arthritis, and cancer-;as they age. Gorbunova and Seluanov have devoted many years of research to understanding the unique mechanisms that naked mole rats use to guard themselves against aging and diseases.

The researchers previously discovered that HMW-HA is one mechanism liable for naked mole rats’ unusual resistance to cancer. In comparison with mice and humans, naked mole rats have about ten times more HMW-HA of their bodies. When the researchers removed HMW-HA from naked mole rat cells, the cells were more prone to form tumors.

Gorbunova, Seluanov, and their colleagues desired to see if the positive effects of HMW-HA may be reproduced in other animals.

Transferring a gene that produces HMW-HA

The team genetically modified a mouse model to supply the naked mole rat version of the hyaluronan synthase 2 gene, which is the gene liable for making a protein that produces HMW-HA. While all mammals have the hyaluronan synthase 2 gene, the naked mole rat version appears to be enhanced to drive stronger gene expression.

The researchers found that the mice that had the naked mole rat version of the gene had higher protection against each spontaneous tumors and chemically induced skin cancer. The mice also had improved overall health and lived longer in comparison with regular mice. Because the mice with the naked mole rat version of the gene aged, that they had less inflammation in numerous parts of their bodies-;inflammation being a trademark of aging-;and maintained a healthier gut.

While more research is required on exactly why HMW-HA has such useful effects, the researchers consider it’s because of HMW-HA’s ability to directly regulate the immune system.

A fountain of youth for humans?

The findings open latest possibilities for exploring how HMW-HA may be used to enhance lifespan and reduce inflammation-related diseases in humans.

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

They consider they’ll accomplish this through two routes: either by slowing down degradation of HMW-HA or by enhancing HMW-HA synthesis.

“We have already got identified molecules that decelerate hyaluronan degradation and are testing them in pre-clinical trials,” Seluanov says. “We hope that our findings will provide the primary, but not the last, example of how longevity adaptations from a long-lived species may be adapted to learn human longevity and health.”

Source:

Journal reference:

Zhang, Z., et al. (2023). Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice. Nature. doi.org/10.1038/s41586-023-06463-0.