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

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 co

SUBMITTER: Jenkins NL 

PROVIDER: S-EPMC7373428 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature