Senescent cells exhibit a pro-inflammatory phenotype, and are thought to accelerate ageing and the onset of age-related diseases. Baar et al. report a key role for forkhead box protein O4 (FOXO4) in maintaining senescent cell viability. In vitro, a FOXO4-derived peptide designed to inhibit the interaction of this transcription factor with the tumour suppressor p53 reduced senescent cell viability through p53-mediated cell-intrinsic apoptosis. In mice, the FOXO4-derived peptide counteracted doxorubicin-induced chemotoxicity and restored fitness, fur density and renal function in models of ageing.
References
Baar, M. P. et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169, 132–147 (2017)
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Crunkhorn, S. FOXO4 inhibition eliminates senescent cells. Nat Rev Drug Discov 16, 386 (2017). https://doi.org/10.1038/nrd.2017.98
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DOI: https://doi.org/10.1038/nrd.2017.98