Dietary supplement vanadyl sulfate selectively eliminates senescent cells

During human evolution, lifestyles including dietary choices have had a major impact on shaping of human physiology and health, including aging. However, the underlying mechanisms remain largely unknown. Here, we use a blood nutrient compound library-based screening approach to demonstrate that dietary supplement vanadyl sulfate (VS) selectively induces cell death in senescent cells and ameliorates phenotypes of aging and age-related disorders in vivo. Integrated chemical biology and multi-omics studies reveal that senescent cells are specifically sensitive to VS due to reduced cysteine reactivity with accumulated glutathione disulfide. VS selectively inactivates reactive cysteines on proteins to induce formation of incorrect disulfide bonds in senescent cells with imbalanced cellular redox status, causing aberrant protein misfolding and aggregation and eventual cell death. Our findings uncover a new senolytic mechanism to mitigate age-related disorders and reshape human physiology. Overall design: KAS-seq of induced senescent BJ cells to detect transcriptional responses of VS treatment.