We’ve discovered another reason why naked mole rats live for so long

Naked mole rats can live up to 37 years—far exceeding the lifespan of other rodents of comparable size. What is the key to their extraordinary longevity? A potential factor may be a variant of an immune protein that enhances DNA repair.

This discovery holds the promise of new therapies aimed at prolonging human lifespans, according to Zhiyong Mao of Tongji University in Shanghai, China. It also further supports the theory that the accumulation of genetic mutations due to ineffective DNA repair contributes significantly to aging.

The protein in question, known as cGAS, is present in various animals. Its primary role is believed to be signaling when it detects DNA outside a cell’s nucleus, which could indicate cancer or a viral infection.

Interestingly, cGAS is also located within the nucleus. In human and mouse cells, it has been shown to impede DNA repair, increasing mutation rates and cancer risk. The reason for this remains unclear—it may be an unintended consequence rather than an evolved characteristic.

Mao’s research has revealed that the cGAS variant found in naked mole rats has the opposite impact within the nucleus, actually enhancing DNA repair. This phenomenon is attributed to differences in four amino acids in the cGAS protein. Altering these amino acids in mole rat cells negates the DNA repair enhancement, while modifying the human cGAS results in loss of its inhibitory effect on DNA repair.

Furthermore, when the research team genetically modified fruit flies to express the naked mole rat version of cGAS, they lived for roughly 70 days, compared to about 60 days for their unmodified counterparts.

So, could enabling human cells to produce the naked mole rat version of cGAS help us live longer? “Yes, gene editing and mRNA delivery could potentially enhance DNA repair and promote longevity in humans,” stated Mao. However, ensuring sufficient production of the modified cGAS in key cells within our bodies presents a significant challenge, he noted.

Alternatively, another avenue could involve discovering small-molecule drugs that can interact with the human cGAS protein and mimic the behavior of the mole rat variant, according to Mao.

The findings indeed imply that cGAS plays a role in lifespan regulation, asserts Vera Gorbunova from the University of Rochester, New York. Her research team has demonstrated that a molecule known as hyaluronic acid contributes to the exceptional longevity of naked mole rats. “Thus, altering the activity of cGAS through pharmacological or genetic means can yield positive effects on health and lifespan,” she stated.