Uncovering a New Factor Behind the Longevity of Naked Mole Rats

Naked mole rats can live for up to 37 years, significantly outliving other rodents of a similar size. So, what accounts for their remarkable lifespan? Research indicates that variations in immune proteins that enhance DNA repair may play a role, among other elements.

This discovery suggests the potential for developing treatments aimed at increasing human longevity, according to Mao Jiyong from Tongji University in Shanghai, China. This finding also supports the notion that the accumulation of mutations and the inability to repair damaged DNA are primary contributors to aging.

The immune protein in focus is called cGAS, found in many organisms. It is primarily thought to function as an alert mechanism in response to DNA detected outside the nucleus, which could indicate cancer or viral invaders.

Interestingly, cGAS is also found within the cell nucleus. In both humans and mice, it has been shown to hinder DNA repair while elevating mutation rates and cancer risk. The precise reasons for this are still unclear and might be an unintended consequence rather than a beneficial adaptation.

Mao and his team have demonstrated that the cGAS variant present in naked mole rats exhibits the opposite behavior in the nucleus, actively promoting DNA repair. This is linked to differences in four amino acids that constitute the cGAS protein. When these amino acids are altered in a mole rat’s cells, their cGAS loses its ability to facilitate DNA repair. Conversely, modifications to the human cGAS can remove its inhibitory effect on DNA repair.

Additionally, when the researchers genetically modified fruit flies to express the naked mole rat version of cGAS, those flies lived nearly 70 days, in contrast to the approximate 60 days lifespan of the unaltered flies.

So, could we enhance our lifespans by introducing naked mole rat cGAS into human cells? “Yes, employing gene editing and mRNA delivery might provide avenues to enhance DNA repair and increase human longevity,” Mao asserts. However, achieving sufficient levels of the crucial cells to produce the modified cGAS poses a challenge.

Alternatively, researchers could seek small-molecule drugs that can interact with the human cGAS protein, prompting it to act more like its mole rat counterpart, Mao suggests.

This study indicates that cGAS does have an impact on lifespan. Additionally, Vera Gorbunova and her research team at the University of Rochester in New York have discovered that a molecule known as hyaluronic acid also plays a role in the notable longevity of naked mole rats. “[Thus,] altering cGAS activity through pharmacological or genetic strategies could yield beneficial outcomes for health and longevity,” she concludes.