Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type animal fed normal and high glucose diets at different age

Metabolic diseases are strongly associated with endoplasmic reticulum (ER) stress. Upon ER stress, the unfolded protein response (UPR) is activated to limit cellular damage. However, escalating cellular UPR response weakens with age. Here, we show that 5-day-old Caenorhabditis elegans fed a bacteria diet with 2% glucose (high glucose diet, HGD-5) extend their lifespan while shortening the lifespan of 1-day-old (HGD-1) animals. We observed a metabolic shift in HGD-1 as glucose and fertility synergistically prolonged the lifespan of HGD-5, independently of DAF-16. Notably, we identified that UPR stress sensors ATF-6 and PEK-1 extended the longevity of HGD-5 worms, while the ire-1 ablation drastically increased HGD-1 lifespan. Based on these observations, we postulate that HGD activates the otherwise quiescent UPR in aged worms to overcome ageing-related stress and restore ER homeostasis. In contrast, young animals subjected to HGD provokes unresolved ER stress, conversely leading to a detrimental stress response. Wild type (WT, N2) C. elegans mRNA profiles of day 8 adulthood fed normal OP50 diet (ND) or supplemented with 2% glucose at day 1 (HGD-1) or day 5 (HGD-5) of adulthood

代谢疾病与内质网（endoplasmic reticulum, ER）应激存在强相关性。当发生内质网应激时，未折叠蛋白反应（unfolded protein response, UPR）会被激活以限制细胞损伤。然而，随着机体衰老，细胞的UPR应答能力会逐渐衰退。本研究显示，喂食含2%葡萄糖的细菌日粮（高葡萄糖日粮，HGD-5）的5日龄秀丽隐杆线虫（Caenorhabditis elegans）寿命得以延长，而喂食相同日粮的1日龄秀丽隐杆线虫（HGD-1）寿命则缩短。我们观察到HGD-1组发生了代谢重编程；同时葡萄糖与生育力可协同延长HGD-5组线虫的寿命，且该调控过程不依赖于DAF-16。值得注意的是，我们发现内质网应激感受器ATF-6与PEK-1可延长HGD-5组线虫的寿命，而敲除ire-1则会显著延长HGD-1组线虫的寿命。基于上述观察结果，我们提出假说：高葡萄糖日粮可激活衰老线虫中原本处于静息状态的UPR，以克服衰老相关应激并恢复内质网稳态。与之相反，高葡萄糖日粮会诱导年轻线虫出现无法缓解的内质网应激，进而引发有害的应激反应。本数据集包含成年第8天喂食正常OP50日粮（ND）、或在成年第1天（HGD-1）或第5天（HGD-5）添加2%葡萄糖的野生型（Wild type, WT, N2）秀丽隐杆线虫的mRNA表达谱。