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Jenkins, N.L.* ; James, S.A.* ; Salim, A.* ; Sumardy, F.* ; Speed, T.P.* ; Conrad, M. ; Richardson, D.R.* ; Bush, A.I.* ; McColl, G.*

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

eLife 9:e56580 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Biochemistry ; C. Elegans ; Chemical Biology ; Ferroptosis ; Fitness ; Frailty ; Glutathione ; Iron ; Lifespan; Cell-death; Life-span; Lipid-peroxidation; Metabolism; Stress; Quantification; Accumulation; Longevity; Evolution; Chelators
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Journal eLife
Quellenangaben Volume: 9, Issue: , Pages: , Article Number: e56580 Supplement: ,
Publisher eLife Sciences Publications
Publishing Place Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Reviewing status Peer reviewed