Related Experiment Video
Updated: Dec 22, 2025
SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Identification of SYK inhibitor, R406 as a novel senolytic agent
Hyun-Ji Cho1,2, Eun Jae Yang3, Joon Tae Park4
1Well Aging Research Center, DGIST, Daegu 42988, Korea.
Abstract:
The selective removal of senescent cells by senolytics is suggested as a potential approach to reverse aging and extend lifespan. Using high-throughput screening with replicative senescence of human diploid fibroblasts (HDFs), we identified a novel senolytic drug R406 that showed selective toxicity in senescent cells. Using flow cytometry and caspase expression analysis, we confirmed that R406 caused apoptotic cell death along with morphological changes in senescent cells. Interestingly, R406 altered the cell survival-related molecular processes including the inhibition of phosphorylation of the focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK) in senescent cells. This pattern was not observed in other known senolytic agent ABT263. Correspondingly, apoptotic cell death in senescent cells was induced by simultaneously blocking the FAK and p38 pathways. Taken together, we suggest that R406 acts as a senolytic drug by inducing apoptosis and reducing cell attachment capacity.
Insights
A new senolytic drug, R406, selectively kills senescent cells by inducing apoptosis and inhibiting cell attachment pathways. This discovery offers a potential strategy for aging reversal and lifespan extension.
Area of Science:
- Cellular senescence
- Aging research
- Drug discovery
Background:
- Senescent cells accumulate with age and contribute to aging.
- Senolytics, drugs that clear senescent cells, show promise for age-related diseases.
- Identifying novel senolytics is crucial for therapeutic development.
Purpose of the Study:
- To identify novel senolytic drugs.
- To investigate the mechanism of action of a newly identified senolytic compound, R406.
Main Methods:
- High-throughput screening of senescent human diploid fibroblasts (HDFs).
- Flow cytometry and caspase expression analysis to assess apoptosis.
- Western blot analysis to examine molecular pathways (FAK, p38 MAPK).
Main Results:
- R406 demonstrated selective toxicity towards senescent HDFs.
- R406 induced apoptotic cell death and morphological changes in senescent cells.
- R406 inhibited focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation, unlike ABT263.
Conclusions:
- R406 is a novel senolytic agent that induces apoptosis in senescent cells.
- R406 functions by inhibiting FAK and p38 MAPK pathways, reducing cell attachment.
- R406 represents a potential therapeutic candidate for aging and age-related conditions.
More Related Videos
08:49Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
09:32Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
Published on: October 17, 2025
