Graphical summary. This study employed GPMM and meta-flux analysis to investigate senescence-associated metabolic changes across 12 cell lines representing four types of cellular senescence: replicative (Rep), irradiation-induced (IR), ROS-induced, and oncogene-induced. The results revealed that RS and ROIS share similar metabolic features, characterized by dysregulated lipid metabolism and the mevalonate pathway. In contrast, IIS and OIS exhibit distinct metabolic features. Experimental validation in HDF cell lines and C. elegans models supported these findings. Rescuing metabolic dysregulation caused by ROIS and RS in the mevalonate pathway extends the lifespan of C. elegans. This study highlights the metabolic heterogeneity and commonalities across different types of senescence, providing valuable insights for translational applications in aging and senescence research. This graphical summary was created using BioRender with the publication license ID of PH27RO8LR0.