Institute of Biopharmaceutical Sciences, Yang-Ming University, Taipei, Taiwan.
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Aging Cell. 2020 Jun;19(6):e13157. doi: 10.1111/acel.13157. Epub 2020 May 20.
Stress granules (SGs) are nonmembranous organelles that are dynamically assembled and disassembled in response to various stressors. Under stressed conditions, polyadenylated mRNAs and translation factors are sequestrated in SGs to promote global repression of protein synthesis. It has been previously demonstrated that SG formation enhances cell survival and stress resistance. However, the physiological role of SGs in organismal aging and longevity regulation remains unclear. In this study, we used TIAR-1::GFP and GTBP-1::GFP as markers to monitor the formation of SGs in Caenorhabditis elegans. We found that, in addition to acute heat stress, SG formation could also be triggered by dietary changes, such as starvation and dietary restriction (DR). We found that HSF-1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK-eEF2K signaling is required for starvation and DR-induced SG formation but not heat shock. Moreover, our data suggest that this AMPK-eEF2K pathway-mediated SG formation is required for lifespan extension by DR, but dispensable for the longevity by reduced insulin/IGF-1 signaling. Collectively, our findings unveil a novel role of SG formation in DR-induced longevity.
应激颗粒（SGs）是一种无膜细胞器，可动态组装和拆卸，以响应各种应激源。在应激条件下，多聚腺苷酸化的 mRNA 和翻译因子被隔离在 SGs 中，以促进蛋白质合成的全局抑制。先前的研究表明，SG 的形成增强了细胞的存活和应激抗性。然而，SG 在生物体衰老和长寿调控中的生理作用尚不清楚。在本研究中，我们使用 TIAR-1::GFP 和 GTBP-1::GFP 作为标记来监测秀丽隐杆线虫中 SG 的形成。我们发现，除了急性热应激外，SG 的形成还可以被饮食变化（如饥饿和饮食限制（DR））触发。我们发现，HSF-1 对于急性热休克和饥饿引起的 SG 形成是必需的，但对于 DR 引起的 SG 形成则不是必需的，而 AMPK-eEF2K 信号通路对于饥饿和 DR 诱导的 SG 形成是必需的，但对于热休克则不是必需的。此外，我们的数据表明，这种 AMPK-eEF2K 通路介导的 SG 形成对于 DR 诱导的寿命延长是必需的，但对于减少胰岛素/IGF-1 信号通路的长寿则是可有可无的。总之，我们的研究结果揭示了 SG 形成在 DR 诱导的长寿中的新作用。
