Changes in ferrous iron and glutathione promote ferroptosis and frailty in aging Caenorhabditis elegans
Journal Title
Elife
Publication Type
Journal Article
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.
Publisher
eLife Sciences
Research Division(s)
Bioinformatics
PubMed ID
32690135
Open Access at Publisher's Site
https://doi.org/10.7554/eLife.56580
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-08-05 10:02:58
Last Modified: 2020-08-05 10:13:25
An error has occurred. This application may no longer respond until reloaded. Reload 🗙