In a groundbreaking achievement, researchers at the University of Rochester have successfully transplanted a longevity gene from naked mole rats to mice, resulting in improved health and an extended lifespan for the mice. Naked mole rats, renowned for their extended lifespans and remarkable resistance to age-related ailments, have long intrigued the scientific community. By introducing a specific gene responsible for enhanced cellular repair and protection into mice, the Rochester scientists have unveiled promising avenues for unraveling the mysteries of aging and potentially extending human lifespan.

Vera Gorbunova, the Doris Johns Cherry Professor of biology and medicine at Rochester, states, “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.”

In a study published in Nature, Gorbunova, along with Andrei Seluanov, a biology professor, and their research team, revealed their success in transferring a gene responsible for producing high molecular weight hyaluronic acid (HMW-HA) from naked mole rats to mice. This led to enhanced health and an approximate 4.4 percent increase in the median lifespan of the mice.

Naked mole rats are mouse-sized rodents known for their exceptional longevity, living up to 41 years, nearly ten times longer than rodents of similar size. Remarkably, they resist age-related diseases that often afflict other species, including neurodegeneration, cardiovascular disease, arthritis, and cancer. Gorbunova and Seluanov have dedicated years to investigating the distinctive mechanisms employed by naked mole rats to shield themselves against aging and diseases. HMW-HA, they discovered, plays a pivotal role in the rats’ remarkable cancer resistance. Naked mole rats possess approximately ten times more HMW-HA in their bodies than mice and humans. Removing HMW-HA from naked mole rat cells increased the likelihood of tumor formation.

To examine whether the beneficial effects of HMW-HA could be replicated in other animals, the team genetically modified a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, responsible for producing HMW-HA. While all mammals possess this gene, the naked mole rat version appears to be enhanced for stronger gene expression. Mice with the naked mole rat version of the gene demonstrated improved protection against both spontaneous tumors and chemically induced skin cancer. They also enjoyed enhanced overall health and extended lifespans compared to regular mice. As these mice aged, they exhibited less inflammation throughout their bodies, a hallmark of aging, and maintained healthier gut health.

Although further research is required to fully comprehend why HMW-HA yields such beneficial effects, the researchers believe it is due to HMW-HA’s capacity to directly regulate the immune system.

These findings introduce new possibilities for exploring how HMW-HA could enhance human lifespan and reduce inflammation-related diseases. Gorbunova explains, “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. Our next goal is to transfer this benefit to humans.” This can be achieved through two approaches: slowing down the degradation of HMW-HA or enhancing HMW-HA synthesis.

Seluanov adds, “We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials. 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.”

By Impact Lab