Overview

• Science reports that four amino-acid substitutions in naked mole-rat cGAS shift the enzyme from suppressing to promoting homologous recombination DNA repair.
• The changes reduce ubiquitination and degradation of cGAS, allowing it to persist at damage sites and strengthen interactions with repair factors FANCI and RAD50.
• CRISPR removal of cGAS in mole-rat cells led to DNA damage accumulation, supporting a direct role in genome maintenance.
• Fruit flies engineered to express the mole-rat cGAS lived about 10 days longer, and AAV delivery to aged mice reduced frailty, hair graying, inflammatory markers, and cellular senescence signals.
• Only two other mammals—the gray squirrel and the blind mole-rat—share the same substitutions, and commentary accompanying the paper highlights promise but calls for further mechanistic and safety studies, including any future gene-editing, mRNA, or small-molecule approaches.