Naked Mole-Rat’s ‘Longevity’ Gene Extends Lifespan and Health of Mice

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They weigh about an ounce, spend their lives underground in sub-Saharan Africa and are unlikely to be making the shortlist for any cute animal calendars, but the naked mole-rat continues to show scientists it has incredible age-resistant biology beneath its pale, wrinkly skin.

Scientists from the University of Rochester have had the naked mole-rat (Heterocephalus glaber) in their crosshairs for some time, previously identifying how their unique cellular aging mechanisms lay the foundation for their long lifespans – up to 41 years, during which the females also remain fertile – and resistance to age-related diseases.

Building on that knowledge, the researchers genetically modified mice to produce the naked mole-rat version of the hyaluronan synthase 2 gene, which makes a protein that produces high molecular weight hyaluronic acid (HMW-HA). While all mammals have hyaluronan synthase 2, the naked mole-rat’s version is somehow enhanced, driving stronger gene expression.

The modification directly led to the improved overall health of the aging mice and an approximate 4.4% increase in median lifespan.

“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,” said Vera Gorbunova, professor of biology and medicine at Rochester.

While this increase may not seem much, particularly in an animal with a lifespan of under 18 months, it’s not insignificant. For a human, the same increase would see an 80-year-old gain 3.5 more years.

But it’s not just numbers on the board. The mice with the naked mole-rat’s version of the hyaluronan synthase 2 gene had better protection against cancers, had less inflammation in different parts of their body, and had a much healthier gut.

Naked mole-rats have about 10 times more HMW-HA than humans; when it was removed from their bodies, their cells were more likely to form cancerous tumors. While more research is needed, the scientists believe the benefits stem from HMW-HA’s direct regulation of the immune system.

“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 said. “Our next goal is to transfer this benefit to humans.”

“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,” said Andrei Seluanov, a professor of biology at Rochester.

The research was published in the journal Nature.

Source: News Atlas