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

eLife

Fransisca Sumardy¹  Ashley I Bush²  Terence P Speed³  Simon A James⁴  Des R Richardson⁵  Agus Salim⁶  Gawain McColl⁷  Nicole L Jenkins⁸  Marcus Conrad⁸ 

[1] Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;Department of Mathematics and Statistics, University of Melbourne, Melbourne, Australia;Melbourne School of Population and Global Health, and School of Mathematics and Statistics, University of Melbourne, Melbourne, Australia;Australian Synchrotron, ANSTO, Clayton, Australia;Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;Department of Mathematics and Statistics, La Trobe University, Bundoora, Australia;Helmholtz Zentrum München, Institute of Metabolism and Cell Death, Neuherberg, Germany;Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health and University of Melbourne, Parkville, Australia;

关键词: iron;    ferroptosis;    frailty;    lifespan;    glutathione;    fitness;   

DOI  :  10.7554/eLife.56580

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown