Abstract：
The blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is a cytokine-stimulated pathway that has a crucial role in immune regulation, proliferation, and cytokine production. Therefore, the pathway has recently attracted interest in cellular senescence studies. Here, by using publicly available data, we report that JAK-STAT signaling was suppressed in the BMR in comparison to the mouse. Interestingly, our experimental results showed upregulated Jak1/2 expressions in BMR fibroblasts during the replicative senescence process. The transcriptomic analysis using publicly available data also demonstrated that various cytokines related to JAK-STAT signaling were upregulated in the late passage cells, while some other cytokines such as MMPs and SERPINs were downregulated, representing a possible balance of senescence-associated secretory phenotypes (SASPs) in the BMR. Finally, our proteomics data also confirmed cytokine-mediated signaling activation in senescent BMR fibroblasts. Together, our findings suggest the critical role of JAK-STAT and cytokine-mediated signaling pathways during cellular senescence, pointing to the possible contribution of divergent inflammatory factors to the superior resistance of aging and cancer in BMRs.
摘要：
盲摩尔鼠（BMR），一种长期存活的地下啮齿动物,是衰老和癌症研究的特殊模型，因为它们不显示与年龄相关的表型或肿瘤形成。Janus激酶-信号转导和转录激活因子（JAK-STAT）信号传导是细胞因子刺激的途径，在免疫调节中起着至关重要的作用。扩散,和细胞因子的产生。因此,该途径最近引起了细胞衰老研究的兴趣。这里,通过使用公开可用的数据，我们报道,与小鼠相比,JAK-STAT信号在BMR中受到抑制.有趣的是,我们的实验结果表明，在复制衰老过程中，BMR成纤维细胞中Jak1/2的表达上调。使用公开数据的转录组学分析还表明，与JAK-STAT信号相关的各种细胞因子在晚期传代细胞中上调，而其他一些细胞因子如MMPs和SERPINs被下调，代表BMR中衰老相关分泌表型（SASPs）的可能平衡。最后,我们的蛋白质组学数据也证实了衰老BMR成纤维细胞中细胞因子介导的信号激活.一起,我们的研究结果表明JAK-STAT和细胞因子介导的信号通路在细胞衰老过程中的关键作用，指出不同的炎症因子可能对BMR的衰老和癌症的优越抗性做出贡献。
