An effective system for senescence modulating drug development using quantitative high-content analysis and high-throughput screening

Study of cellular senescence is critical in aging research and anti-senescence therapy drug development. Current methods for the evaluation of the widely accepted cellular senescence marker senescence-associated beta galactosidase (SA-β-gal) activity assay rely on bright-field imaging, which is non-quantitative and tedious to perform. We have developed an effective and reproducible multiplex high-content analysis system for high-throughput screen and evaluation of senescence modulators. The IC₅₀ or EC₅₀ of the senescence modulators on fibroblasts were determined, which are essential for drug development and have not been able done before. In a single high-throughput screen, all three types of senomorphic, senolytic, and seno-inducing agents can be evaluated effectively. Using our system, we have identified new molecular entities that modulate MMC-induced senescence in fibroblasts through potential new cellular targets.