Journal article

Changes in ferrous iron and glutathione promote ferroptosis and frailty in aging Caenorhabditis elegans

Nicole L Jenkins, Simon A James, Agus Salim, Fransisca Sumardy, Terence P Speed, Marcus Conrad, Des R Richardson, Ashley Bush, Gawain McColl



All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termed ferroptosis, all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in Caenorhabditis elegans. Here, we show that glutathione depletion is coupled to ferrous iron elevation in these animals, and that both occur in late life to prime cells for ferroptosis. We demonstrate that blocking ferroptosis, either by inhibition of lipid peroxidation or by limiting iron retention, mitigates age-related cell death and markedly increases lifespan and healthspan. Temporal scaling of lifespan is not evident when ferroptosis is inhibited, consistent with this cell death p..

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Awarded by Australian Research Council

Funding Acknowledgements

Australian Research Council DP130100357 Ashley I Bushr Australian Research Council DP180101248 Gawain McCollr University of Melbourne Gawain McCollr The Miller Foundation Ltd Gawain McCollr The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.