Gene Transfer Shows Promise in Increasing Longevity

Successful longevity gene transfer from naked mole rats to mice improved the health and lifespan of the animals.

Naked mole rats, rodents the size of a mouse, have long captured scientists' attention due to their exceptional longevity. They can live up to 41 years, which is nearly ten times as long as similar-size rodents, and rarely contract diseases as they age.

Researchers at the University of Rochester have previously discovered that high-molecular-weight hyaluronic acid (HMW-HA) may be responsible for mole rats' resistance to cancer. Our bodies naturally produce hyaluronic acid that improves joints' function and helps keep skin hydrated, among other benefits.

Mole rats have about ten times more HMW-HA than humans and mice. When the researchers removed HMW-HA from mole rats' cells, they were more likely to develop tumors.

In a new study published in Nature, the researchers genetically modified a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene. This gene is responsible 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 transfer of the mole rat version of the synthase 2 gene increased the median lifespan in mice by 4.4% and provided better protection against spontaneous tumors and chemically induced skin cancer. As the mice that underwent gene transfer aged, their bodies had less inflammation — considered a hallmark of aging — and maintained a healthier gut.

Researchers say the observed effects may be due to HMW-HA's ability to directly regulate the immune system. However, more research is needed.

The research team is now planning to explore how HMW-HA could also be used to increase lifespan and reduce inflammation-related diseases in humans. They say it could be accomplished either by slowing down the degradation of HMW-HA or by enhancing HMW-HA synthesis.

"We have already 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," says the study's author, Andrei Seluanov, a professor of biology at the University of Rochester.

Inflammation is a normal part of the body's defense to injury or infection. However, if prolonged or occurs in healthy tissues, inflammation can contribute to the development of a wide range of diseases, including some types of cancers, neurodegenerative illnesses, and autoimmune and cardiovascular diseases.

While scientists are still looking for a silver bullet that could lead to healthier and longer lives, research in mice provides insights into how to stop or even reverse aging and related diseases in humans.

For example, a recent trio of studies identified a blood factor called platelet factor 4 (PF4) that may explain why young blood transfusion, exercise, and the longevity hormone klotho are effective interventions against cognitive decline.

However, it may take years until gene transfer and other longevity-increasing tools will be used in humans. Meanwhile, healthy lifestyle choices, such as a balanced diet or exercise, can improve the quality of life.