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Update, October 18: After publication, Rochelle Buffenstein shared a new observation from her bioinformatics checks: the same cGAS amino-acid substitutions also appear in guinea pigs, a species that is neither long-lived nor notably cancer-resistant. She writes, “the effect of these mutations is probably not very large despite the findings in flies.”

As discussed in the piece below, cGAS is unlikely to be the sole reason for naked mole-rats’ exceptional longevity. This finding strengthens the view that their resistance to aging and disease depends on multiple interacting mechanisms, not a single mutation.

Four small differences in a single enzyme may help explain one of biology’s strangest outliers: the naked mole-rat’s ability to live for over thirty years without obvious signs of aging.

In a new Science paper, researchers in Shanghai, led by Zhiyong Mao, report that the naked mole-rat’s version of an enzyme called cGAS carries four amino-acid substitutions that appear to make its cells unusually good at repairing DNA damage, a primary hallmark of aging. When the team expressed the mole-rat version of cGAS in fruit flies, the flies lived about ten days longer - quite the extension for an animal that normally survives only two months.

It’s a modest evolutionary tweak with big consequences - one that might help explain why these rodents stay healthy long after other mammals their size are long gone.

“This is an excellent article,” Rochelle Buffenstein*, the biologist who first established naked mole-rats as models for studying aging, tells LEVITY.