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

Naked mole rats live up to 37 years, much longer than other rodents of the same size. What is the secret of their longevity? Among other factors, this could be due to a different type of immune protein that promotes DNA repair

This discovery could lead to treatments that extend human lifespan, for example Qi Yong Mao At Tongji University in Shanghai, China. It is also further evidence supporting the idea that the accumulation of mutations – the failure to repair damaged DNA – is one of the main causes of aging.

The immune protein in question, called cGAS, is present in many animals. Its main function is thought to sound an alarm when it detects DNA outside the cell nucleus, which could be a sign of cancer or a viral attack.

But cGAS is also present in the nucleus of cells. In humans and mice, it has been shown to inhibit DNA repair, increasing the mutation rate and cancer risk. The exact cause is not clear – it could be an unwanted side effect rather than a developed function.

Mao’s team has now shown that the version of cGAS found in naked mole rats has the opposite effect in the nucleus, actually promoting DNA repair. This is due to differences in four of the amino acids that make up the cGAS protein. If these four amino acids are changed in mole rat cells, the animal’s cGAS no longer promotes DNA repair. Conversely, if these elements are changed in the human version of cGAS, the protein no longer prevents DNA repair.

Furthermore, when the team genetically engineered fruit flies to produce the naked mole rat version of cGAS, they lived for about 70 days, compared to about 60 days for unedited flies.

Could human cells producing naked mole rats extend our lives? “Yes, gene editing and mRNA delivery could be potential ways to improve DNA repair and promote longevity in humans,” says Mao. But getting enough master cells in our bodies to produce modified cGAS won’t be easy, he says.

Another way, Mao says, is to find small-molecule drugs that interact with the human cGAS protein and make it behave like a mole rat.

The study does indicate that cGAS affects lifespan, the study says Vera Gorbunova at the University of Rochester in New York, whose team has shown that a molecule called hyaluronic acid also contributes to the longevity of naked mole rats. “[So] “Modulating cGAS activity by pharmacological or genetic means could have beneficial effects on health and lifespan,” she says.

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