The naked mole rat’s molecular secrets to a long life

Behold the biological beauty of the naked mole rat. These acid-insensitive, cancer-resistant, oft-oxygen-deprived rodents live around 37 years—10 times as long as their relatives of similar size. After some biochemical sleuthing, scientists now think they have identified one of the molecular mechanisms that gives these wrinkly darlings their longevity (Science 2025, DOI: 10.1126/science.adp5056).Researchers led by Tongji University’s Ying Jiang and Zhiyong Mao think the key lies within an enzyme called cyclic guanosine monophosphate–adenosine monophosphate synthase, or cGAS. This enzyme helps regulate repairs to double-strand breaks in DNA through a process known as homologous recombination.In people, cGAS suppresses DNA repair; in naked mole rats, it appears to enhance the ability to repair genetic damage related to aging. Jiang and Mao’s team pinpointed a difference in four amino acids between human cGAS and naked mole rat cGAS. The variation reduces ubiquitination and degradation of the rodent’s cGAS, so the enzyme hangs around longer after DNA damage in order to recruit DNA-repair factors.The team genetically engineered fruit flies to make naked mole rat cGAS and found that they lived 70 days—10 days longer than control fruit flies, which don’t make cGAS. Flies engineered to make human cGAS lived about 50 days.The team also gave naked mole rat cGAS to mice via gene therapy. Mice that got the treatment were less frail, had less gray hair, and showed other signs of being healthier than mice that didn’t get the gene therapy.In an email to C&EN, Mao says scientists might be able to boost lifespan