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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)
Verlagsversion Forschungsdaten DOI PMC
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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23
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Biochemistry ; C. Elegans ; Chemical Biology ; Ferroptosis ; Fitness ; Frailty ; Glutathione ; Iron ; Lifespan; Cell-death; Life-span; Lipid-peroxidation; Metabolism; Stress; Quantification; Accumulation; Longevity; Evolution; Chelators
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Zeitschrift eLife
Quellenangaben Band: 9, Heft: , Seiten: , Artikelnummer: e56580 Supplement: ,
Verlag eLife Sciences Publications
Verlagsort Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Metabolism and Cell Death (MCD)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-506900-001
DOI 10.7554/eLife.56580
WOS ID WOS:000557274700001
Scopus ID 85088351485
PubMed ID 32690135
Erfassungsdatum 2020-10-02
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