>>12515649All 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
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.
Pic related
>Inhibiting ferroptosis extends Caenorhabditis elegans lifespan.Treatment with both Lip-1 and SIH extend lifespan. (A) Representative Kaplan-Meier survival curve from C. elegans treated with vehicle control (Ctl, median survival 7 days, death events n = 88); Lip-1 (median survival 13 days, Log-rank test p<0.001, n = 103) and SIH (median survival 14 days, p<0.001, n = 71) at 25°C. (B) Survival curve derived from pooled data from all eight replicate experiments (Ctl n = 709, Lip-1 n = 809, and SIH n = 720; see Supplementary file 4) at 25°C. (C) Plot of hazard (mortality) rate against age at 25°C, derived from meta-analysis of pooled data (presented in B). Both SIH and Lip-1 alter mortality rates relative to control populations and are also distinct from each other. (see Supplementary file 5).
