Hydra vulgaris (Hv) has a high regenerative potential and negligible senescence, as its stem cell populations divide continuously. In contrast, the cold-sensitive H. oligactis (Ho_CS) rapidly develop an aging phenotype under stress, with epithelial stem cells deficient for autophagy, unable to maintain their self-renewal. Here we tested in aging, non-aging and regenerating Hydra the activity and regulation of the ULK1 kinase involved in autophagosome formation. In vitro kinase assays show that human ULK1 activity is activated by Hv extracts but repressed by Ho_CS extracts, reflecting the ability or inability of their respective epithelial cells to initiate autophagosome formation. The factors that keep ULK1 inactive in Ho_CS remain uncharacterized. Hv_Basel1 animals exposed to the ULK1 inhibitor SBI-0206965 no longer regenerate their head, indicating that the sustained autophagy flux recorded in regenerating Hv_AEP2 transgenic animals expressing the DsRed-GFP-LC3A autophagy tandem sensor is necessary. The SBI-0206965 treatment also alters the contractility of intact Hv_Basel1 animals, and leads to a progressive reduction of animal size in Hv_AEP2, similarly to what is observed in ULK1(RNAi) animals. We conclude that the evolutionarily-conserved role of ULK1 in autophagy initiation is crucial to maintain a dynamic homeostasis in Hydra, which supports regeneration efficiency and prevents aging.

Hydra vulgaris (Hv)具有很高的再生潜力和可忽略不计的衰老，因为其干细胞群不断分裂。相比之下，冷敏感的寡头梭菌( Ho_CS ) 在压力下迅速发展为衰老表型，上皮干细胞缺乏自噬，无法维持自我更新。在这里，我们在老化、非老化和再生Hydra 中测试了参与自噬体形成的 ULK1 激酶的活性和调节。在体外激酶测定表明，人类活动ULK1由活化的HV提取物，而是由压抑Ho_CS提取物，反映了它们各自的上皮细胞启动自噬体形成的能力或无能力。在Ho_CS 中使ULK1保持不活动的因素仍未确定。暴露于 ULK1 抑制剂 SBI-0206965 的Hv_Basel1动物不再再生它们的头部，表明在再生Hv_AEP2转基因动物中记录的持续自噬通量是必要的。SBI-0206965 处理还改变了完整Hv_Basel1动物的收缩力，并导致Hv_AEP2中动物大小逐渐减小，类似于在ULK1(RNAi) 中观察到的情况动物。我们得出结论，ULK1 在自噬启动中的进化保守作用对于维持Hydra的动态稳态至关重要，这有助于提高再生效率并防止衰老。