Aging is often accompanied by chronic, low-grade inflammation, termed inflammaging. Recent evidence suggests that the cGAS/STING signaling pathway, which mediates immune sensing of DNA, is a critical driver of senescence and inflammaging. However, the role of this pathway in aging is still far from being understood. In a recent preprint (not peer-reviewed), Ballhysa et al. investigated the role of the cGAS/STING pathway in the African turquoise killifish Nothobranchius furzeri, an emerging model system for studying aging. While the results confirm the conserved role of the cGAS/STING pathway in senescence, inflammation and some aging features, they also show that loss of cGAS/STING function has no effect on killifish lifespan.

After creating fish knockouts (KO) for cGAS and STING, the team isolated primary fibroblast to study the role of cGAS/STING in vitro, notably after senescence activation. Nine days after inducing senescence in the fibroblasts using γ-radiation, the researchers extracted RNA and performed a transcriptomic analysis, which revealed a decrease in the expression of senescence markers in cGAS KO and STING KO cells compared to wild-type (WT) cells. Similarly, the team irradiated young WT and cGAS KO fish with 15 Gy of γ-radiation to assess stress responses in vivo, confirming a decrease in senescence responses in cGAS KO fish compared to WT.

衰老通常伴有慢性、低度炎症，称为炎症。最近的证据表明，介导 DNA 免疫感应的 cGAS/STING 信号通路是衰老和炎症的关键驱动因素。然而，这条途径在衰老中的作用仍远未被理解。在最近的预印本（未经过同行评审）中，Ballhysa 等人研究了 cGAS/STING 通路在非洲绿松石鱼 Nothobranchius furzeri 中的作用，Nothobranchius furzeri 是一种研究衰老的新兴模型系统。虽然结果证实了 cGAS/STING 通路在衰老、炎症和一些衰老特征中的保守作用，但它们也表明 cGAS/STING 功能的丧失对基利鱼的寿命没有影响。

在为 cGAS 和 STING 创建鱼敲除 （KO） 后，该团队分离了原代成纤维细胞，以研究 cGAS/STING 在体外的作用，尤其是在衰老激活后。使用 γ 辐射诱导成纤维细胞衰老 9 天后，研究人员提取了 RNA 并进行了转录组学分析，结果显示与野生型 （WT） 细胞相比，cGAS KO 和 STING KO 细胞中衰老标志物的表达降低。同样，该团队用 15 Gy 的 γ 辐射照射年轻的 WT 和 cGAS KO 鱼，以评估体内的应激反应，证实与 WT 相比，cGAS KO 鱼的衰老反应有所减少。