Changes in ferrous iron and glutathione promote ferroptosis and frailty in aging Caenorhabditis elegans
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James, Simon A
Salim, Agus
Sumardy, Fransisca
Speed, Terence P
Conrad, Marcus
Richardson, Des R
Bush, Ashley
McColl, Gawain
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Abstract
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 process acting at specific life phases to induce organismal frailty, rather than contributing to a constant aging rate. Because excess age-related iron elevation in somatic tissue, particularly in brain, is thought to contribute to degenerative disease, post-developmental interventions to limit ferroptosis may promote healthy aging.
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eLife
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9
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© 2020 Jenkins et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Biochemistry and cell biology
Biological sciences
Biomedical and clinical sciences
Health sciences
Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
CELL-DEATH
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Jenkins, NL; James, SA; Salim, A; Sumardy, F; Speed, TP; Conrad, M; Richardson, DR; Bush, A; McColl, G, Changes in ferrous iron and glutathione promote ferroptosis and frailty in aging Caenorhabditis elegans, eLife, 2020, 9, pp. e56580