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 In a recent preprint (not peer-reviewed), Ballhysa et al.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.
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