同济大学最新Science论文：cGAS的这种突变，可延缓衰老、延长寿命

Core Viewpoint - The research reveals that specific mutations in the cGAS protein of naked mole-rats enhance DNA repair mechanisms, potentially leading to extended lifespan and healthspan, suggesting a new strategy for aging intervention in humans [2][3][9]. Summary by Sections Research Findings - The study identifies four specific amino acid mutations in the cGAS protein of naked mole-rats that convert it from a DNA repair inhibitor to a repair enhancer, thereby promoting DNA repair and delaying aging [3][6]. - Compared to humans and mice, naked mole-rat cGAS improves the efficiency of homologous recombination repair, which is crucial for maintaining genomic stability [6][9]. Mechanism of Action - The mutations in cGAS alter its interaction with ubiquitin, extending its retention time on chromatin after DNA damage, which enhances the formation of complexes necessary for DNA repair [6][9]. - The study demonstrates that the naked mole-rat cGAS mitigates stress-induced cellular aging and organ degeneration, contributing to increased lifespan [6][9]. Experimental Validation - Delivery of naked mole-rat cGAS to aged mice using adeno-associated virus (AAV) alleviated signs of frailty, reduced inflammation markers, and decreased cellular aging indicators, thereby extending healthspan [7][9]. Implications for Human Aging - The findings suggest that mimicking the unique mutations of naked mole-rat cGAS through small molecules or gene editing could offer new avenues for delaying aging and enhancing healthspan in humans [3][9].