Why in news? Two independent studies published in October 2025 have uncovered how naked mole‑rats repair DNA damage more effectively than other mammals. Scientists discovered that subtle changes in a single protein enable these small rodents to maintain genome stability and live far longer than similarly sized animals.
Background
Naked mole‑rats are eusocial creatures native to the Horn of Africa. They live in underground colonies led by a queen and display remarkable physiological traits: resistance to cancer, tolerance of low oxygen and lifespans that can exceed 30 years. Because they rarely show signs of ageing, researchers have long sought to understand the molecular mechanisms underlying their longevity.
New findings
- Modified cGAS protein: In most mammals the cyclic GMP–AMP synthase (cGAS) protein senses foreign DNA and triggers inflammation, inadvertently slowing DNA repair. Researchers found that in naked mole‑rats four amino acids in cGAS have mutated, reducing the protein’s breakdown and enabling it to bind more tightly to DNA‑repair factors such as FANCI and RAD50. This boosts homologous recombination, a repair pathway that fixes double‑strand breaks accurately.
- Experimental evidence: When fruit flies were engineered with the same four amino acid substitutions, they lived nearly ten days longer than controls. Human cells expressing the mole‑rat‑like cGAS repaired radiation‑induced damage more efficiently, whereas depleting cGAS in mole‑rat cells led to DNA lesions accumulating.
- Convergent evolution: Similar cGAS changes were observed in other long‑lived rodents such as blind mole‑rats and grey squirrels, suggesting that evolution may repeatedly fine‑tune this protein to enhance DNA repair and extend life.
Significance
The discovery illustrates how minor tweaks to a single protein can have outsized effects on lifespan. Understanding the mechanism may help scientists develop therapies to enhance DNA repair in humans, potentially mitigating age‑related diseases. More broadly, the work highlights the value of studying unusual species to uncover new biological insights.
Sources: Smithsonian Magazine and Drug Target Review.