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Researchers from the Centre for Molecular Cell Biology contributed to a study of cellular senescence published in the journal Nature Cell Biology.

Cellular senescence is a stress-response state in which cells permanently stop dividing but remain metabolically active, contributing to tissue repair and tumor suppression, while the accumulation of persistent senescent cells can drive ageing and diseases including cancer.

The study comprised a phenotypic screen of a covalent library of ~10,000 compounds to identify senolytics with novel mechanisms of action. Using target deconvolution approaches, including chemical proteomics with alkyne-tagged probes, the researchers identified glutathione peroxidase GPX4 as a key vulnerability of senescent cells. Senescent cells are primed for ferroptosis but rely on GPX4 to suppress toxic lipid peroxidation. Hence, GPX4 inhibition selectively eliminated senescent cells in cellular and in vivo cancer models, highlighting GPX4 inhibition as a promising strategy for targeting cellular senescence.

Reference:

D'Ambrosio, M., White, M.E.H., Gavriil, E.S. et al. Electrophilic compound screening identifies GPX4-dependent ferroptosis as a senescence vulnerability. Nat Cell Biol 28, 915–929 (2026). https://doi.org/10.1038/s41556-026-01921-z