Clock mediates liver senescence by controlling ER stress.

摘要: Accumulated evidence indicates that circadian genes regulate cell damage and senescence in most mammals. Endoplasmic reticulum (ER) stress reactive oxygen species (ROS) longevity many organisms. However, the specific mechanisms of relationship between clock two processes organisms are poorly understood. Here, we show Clock-mediated Pdia3 expression is required to sustain oxidative reagents ER stress. First, ROS strongly activated liver tissue Clock∆19 mutant mice, which exhibit a significant aging phenotype. Next, transcription mediated by gene Clock, but this process affected due low affinity E-box motif promoter. Finally, ablation with siRNA causes sustained phosphorylation PERK eIF1α, resulting exaggerated up-regulation UPR target increased apoptosis as well ROS. Moreover, combined effects result an imbalance homeostasis ultimately lead senescence. Taken together, study identified Clock regulator senescence, will provide reference for clinical prevention aging.