Studying naked mole rats could help us develop new anti-aging strategies
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Naked mole rats live up to 37 years, much longer than other rodents their size. What is the secret of their longevity? Among other factors, this may be due to a variant of an immune protein that speeds up DNA repair.
The discovery could lead to treatments that extend human lifespan, scientists say. Zhiyong Mao from Tongji University in Shanghai, China. This is also further evidence supporting the idea that the accumulation of mutations, that is, the inability to repair damaged DNA, is one of the main causes aging.
The immune protein in question, called cGAS, is found in many animals. Its main function is thought to sound the alarm when DNA is detected outside the cell's nucleus, which could be a sign of cancer or a viral attack.
But cGAS is also found in cell nuclei. It has been shown to inhibit DNA repair in humans and mice. increase in mutation rate and cancer risk. It's unclear exactly why – it may be an unwanted side effect rather than a developed feature.
Mao's team has now shown that the version of cGAS found in naked mole rats has the opposite effect in the nucleus, actually speeding up DNA repair. This is due to differences in the four 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 enhances DNA repair. Conversely, if they are altered in the human version of cGAS, the protein no longer inhibits DNA repair.
What's more, when a team of genetically engineered fruit flies created a version of cGAS in naked mole rats, they lived for almost 70 days, compared with about 60 days for unmodified flies.
So could forcing human cells to produce naked mole rat cGAS extend our lives? “Yes, gene editing and mRNA delivery could be potential ways to improve DNA repair and extend human lifespan,” says Mao. But getting enough of the key cells in our bodies to produce the modified cGAS won't be easy, he says.
Another approach might be to find small-molecule drugs that interact with the human cGAS protein and make it behave like a mole rat, Mao says.
Study does suggest cGAS affects lifespan, says Vera Gorbunova at the University of Rochester, New York, whose team showed that A molecule called hyaluronic acid also contributes to the long life of naked mole rats.. “[So] Modulating cGAS activity by pharmacological or genetic means may have beneficial effects on health and lifespan,” she says.
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