Work

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

Year: 2025

Type: article

Abstract: 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. Fluorescent detection of senescence-associated beta-galactosidase (SA-beta-gal) activity, enabling automated high-content drug screening and IC50/EC50 measurement, facilitates senescence research and drug development.

Source: Communications Biology

DOI: 10.1038/s42003-025-08758-6