Naked mole rats gene responsible for prolonged lifespan in mice

This attracted the scientific community which led them to discover a specific gene that enhanced cellular repair and protection in mice. The gene was also accountable for making high molecular weight hyaluronic acid (HMW-HA) from a naked mole rat into mice.

Vera Gorbunova, the Doris Johns Cherry professor of biology and medicine at Rochester said:

“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.”

Researchers were able to improve the mice’s health with nearly a 4.4 percent increase in the median lifespan. 

Past research found that HMW-HA is responsible for the mammal’s resistance to cancer. Naked mole rats have ten times more molecular weight in their bodies in contrast to humans and mice. 

Upon removing HMW-HA from the mammal’s cells, scientists noticed that rats were more likely to develop tumors. The positive effects involving transferring genes with HMW-HA include better protection against spontaneous tumors and chemically induced skin cancer.

To perform this task, researchers created a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, which is the gene responsible for making a protein that produces HMW-HA, the statement said.

The study also found that mice had overall improved health and elongated life compared to mice that didn't receive the molecular weight gene.

The University of Rochester stated that as the mice with the naked mole rat version of the gene aged, they had less inflammation in different parts of their bodies with inflammation being a hallmark of aging, and maintained a healthier gut.

Possibly enhancing human life

Scientists suggest that the new gene discovery could help improve human lifespan and possibly reduce inflammation-related diseases.

Gorbunova said, “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.”

She added that the team’s next goal is to transfer this benefit to humans which could be accomplished through two courses – deterioration of HMW-HA could be slowed or HMW-HA synthesis could be improved significantly.

Andrei Seluanov, a professor of biology stated: “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.”

The study was published on 23 August in the journal – Nature.

Study abstract:

Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and possibly to the longevity of the longest-lived rodent—the naked mole-rat1,2. To study whether the benefits of HMM-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHas2). nmrHas2 mice showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHas2 mice shifted towards that of longer-lived species. The most notable change observed in nmrHas2 mice was attenuated inflammation across multiple tissues. HMM-HA reduced inflammation through several pathways, including a direct immunoregulatory effect on immune cells, protection from oxidative stress and improved gut barrier function during ageing. These beneficial effects were conferred by HMM-HA and were not specific to the nmrHas2 gene. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exported to other species, and open new paths for using HMM-HA to improve lifespan and healthspan.