Citation | Schiavi A, Salveridou E, Brinkmann V, Shaik A, Menzel R, Kalyanasundaram S, Nygard S, Nilsen H, Ventura N. Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players. iScience, 2023. |
PubMed ID | 37020951 |
Short Description | Mitochondria hormesis delays aging and associated diseases in Caenorhabditis elegans impacting on key ferroptosis players. GEO Record: GSE225776 Platform: GPL19230 Download gene-centric, log2 transformed data: WBPaper00065197.ce.mr.csv |
# of Conditions | 30 |
Full Description | Excessive iron accumulation or deficiency leads to a variety of pathologies in humans and developmental arrest in the nematode Caenorhabditis elegans. Instead, sub-lethal iron depletion extends C. elegans lifespan. Hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage across species but it has low feasible application. In this study, we assessed the potential beneficial effects of genetic and chemical interventions acting via mild iron instead of oxygen depletion. We show that limiting iron availability in C. elegans through frataxin silencing or the iron chelator bipyridine, similar to hypoxia preconditioning, protects against hypoxia-, age-, and proteotoxicity-induced neuromuscular deficits. Mechanistically, our data suggest that the beneficial effects elicited by frataxin silencing are in part mediated by counteracting ferroptosis, a form of non-apoptotic cell death mediated by iron-induced lipid peroxidation. This is achieved by impacting on different key ferroptosis players and likely via gpx-independent redox systems. We thus point to ferroptosis inhibition as a novel potential strategy to promote healthy aging. Experimental Details: WBPaper00065197:N2_day4_rep1 WBPaper00065197:N2_day4_rep2 WBPaper00065197:N2_day4_rep3 WBPaper00065197:N2_day4_rep4 WBPaper00065197:N2_day4_rep5 WBPaper00065197:N2_day7_rep1 WBPaper00065197:N2_day7_rep2 WBPaper00065197:N2_day7_rep3 WBPaper00065197:N2_day7_rep4 WBPaper00065197:N2_day7_rep5 WBPaper00065197:N2_day14_rep1 WBPaper00065197:N2_day14_rep2 WBPaper00065197:N2_day14_rep3 WBPaper00065197:N2_day14_rep4 WBPaper00065197:N2_day14_rep5 WBPaper00065197:frh-1(RNAi)_day4_rep1 WBPaper00065197:frh-1(RNAi)_day4_rep2 WBPaper00065197:frh-1(RNAi)_day4_rep3 WBPaper00065197:frh-1(RNAi)_day4_rep4 WBPaper00065197:frh-1(RNAi)_day4_rep5 WBPaper00065197:frh-1(RNAi)_day7_rep1 WBPaper00065197:frh-1(RNAi)_day7_rep2 WBPaper00065197:frh-1(RNAi)_day7_rep3 WBPaper00065197:frh-1(RNAi)_day7_rep4 WBPaper00065197:frh-1(RNAi)_day7_rep5 WBPaper00065197:frh-1(RNAi)_day14_rep1 WBPaper00065197:frh-1(RNAi)_day14_rep2 WBPaper00065197:frh-1(RNAi)_day14_rep3 WBPaper00065197:frh-1(RNAi)_day14_rep4 WBPaper00065197:frh-1(RNAi)_day14_rep5. |
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