Overview
- A Science paper published Oct. 9 identifies four amino-acid substitutions in naked mole-rat cGAS that shift its nuclear activity to enhance high-fidelity homologous recombination repair.
- The variant resists ubiquitination and degradation, allowing cGAS to persist after DNA damage and increasing interactions with repair factors FANCI and RAD50.
- Swapping the four residues removed the repair advantage in mole-rat cells and reduced the inhibitory effect of human cGAS, directly linking the substitutions to function.
- Fruit flies expressing the mole-rat variant lived about 70 days versus roughly 60 for controls, and AAV delivery to aged mice reduced frailty, hair graying, and inflammatory markers including IgG and IL-6.
- Authors propose gene editing, mRNA delivery, or small molecules to mimic the effect, while a companion Perspective urges broader cross-species validation and safety studies.