Anti-aging requires interventions capable of simultaneously targeting multiple aging-associated processes to achieve comprehensive rejuvenation. Here, we report that Senoversus, a dual-factor combination of CHIR99021 and bFGF, robustly reverses aging phenotypes compared with either factor alone. In diverse senescence models, Senoversus restores proliferative capacity, suppresses senescence-associated phenotypes, and maintains a rejuvenated cellular state while preserving cellular identity. In naturally aged mice, Senoversus treatment extends both median and mean lifespan by ~20%, accompanied by systemic improvements in physiological functions. Multi-omics analyses reveal that Senoversus induces coordinated remodeling of aging-associated transcriptional and epigenetic states across multiple organs. Specifically, Senoversus broadly suppresses inflammatory, immune, and other aging-associated signaling pathways while activating pathways involved in metabolism, tissue regeneration, and cellular homeostasis through remodeling of transcription factor regulatory networks and their downstream target genes. Together, our findings establish Senoversus as a pharmacological rejuvenation strategy and provide a promising framework for therapeutic intervention to promote healthy aging.