Naked mole-rats can live up to 37 years despite their small size. This is the reason why researchers turned their attention to these creatures to further expand existing understanding about the aging process and longevity. Yu Chen et al. specifically examined how molecular adaptations may protect the cells of these animals from aging-related deterioration.
Aging in most mammals involves the steady accumulation of DNA damage. This eventually leads to malfunctioning cells, rising mutation rates, and diminished organ resilience. Scientists have long believed that organisms capable of maintaining genetic integrity over long periods must depend on unusually efficient repair systems to preserve function.
The research team particularly set their attention on a specific protein known as cyclic GMP AMP synthase or cGAS. According to previous studies, in humans and mice, this protein normally detects misplaced DNA within the cell and triggers inflammatory responses that can inadvertently limit the precision and speed of genetic repair during aging.
A comparison of this protein in mole-rats with versions found in humans and mice resulted in the identification of 4 amino acid substitutions unique to the long-lived rodents. These seemingly subtle genetic differences appeared to convert the cGAS protein from an obstacle to a facilitator of DNA maintenance that alters how stress signals influence cellular behavior.
The researchers test this molecular advantage by inserting the naked mole-rat version of this protein into cultured cells from mice and humans. The modified cells displayed stronger genetic repair activity and showed fewer traits commonly associated with aging. This suggests that the altered protein remains effective outside its native species.
Broader testing involved using fruit flies that were genetically engineered to express the naked mole-rat protein. These flies lived about 10 days longer than their unmodified counterparts under standardized experimental conditions. This is a substantial extension relative to typical lifespans observed in research laboratories for that model organism.
Researchers then applied a particular gene therapy strategy in mice using the emerging concepts and techniques. Mice treated with the naked mole-rat cGAS showed less graying of fur, reduced frailty, and fewer senescent cells across multiple organs when compared with untreated mice evaluated under the same environmental and dietary conditions.
Scientists emphasize that moving from laboratory insight to human application will require patience, caution, and rigorous testing. The discovery that a single protein variant can stabilize the genome without triggering harmful inflammatory responses still offers a novel direction for addressing age-related decline in future medical research.
FURTHER READING AND REFERENCE
- Chen, Y., Chen, Z., Wang, H., Cui, Z., Li, K.-L., Song, Z., Chen, L., Sun, X., Xu, X., Zhang, Y., Tan, L., Yuan, J., Tan, R., Luo, M.-H., Sun, F.-L., Liu, H., Jiang, Y., & Mao, Z. 2025. “A cGAS-mediated Mechanism in Naked Mole-Rats Potentiates DNA Repair and Delays Aging.” Science. 390(6769): DOI: 1126/science.adp5056