title: Manipulation of in vivo iron levels can alter resistance to oxidative stress without affecting ageing in the nematode C. elegans.
abstract: Iron-catalyzed generation of free radicals leads to molecular damage in vivo, and has been proposed to contribute to organismal ageing. Here we investigate the role of free iron in ageing in the nematode Caenorhabditis elegans. Media supplementation with Fe(III) increased free iron levels in vivo, as detected by continuous-wave electron paramagnetic resonance spectroscopy and elevated expression of the iron-sensitive reporter transgene pftn-1::gfp. Increased free iron levels caused elevated levels of protein oxidation and hypersensitivity to tert-butyl hydroperoxide (t-BOOH) given 9 mM Fe(III) or greater, but 15 mM Fe(III) or greater was required to reduce lifespan. Treatment with either an iron chelator (deferoxamine) or over-expression of ftn-1, encoding the iron sequestering protein ferritin, increased resistance to t-BOOH and, in the latter case, reduced protein oxidation, but did not increase lifespan. Expression of ftn-1 is greatly increased in long-lived daf-2 insulin/IGF-1 receptor mutants. In this context, deletion of ftn-1 decreased t-BOOH resistance, but enhanced both daf-2 mutant longevity and constitutive dauer larva formation, suggesting an effect of ferritin on signaling. These results show that high levels of iron can increase molecular damage and reduce lifespan, but overall suggest that iron levels within the normal physiological range do not promote ageing in C. elegans.
authors.affiliation: Institute of Healthy Ageing, and Research Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Valentini
authors.forename: Filipe
authors.initials: F
authors.lastname: Cabreiro
authors.forename: Daniel
authors.initials: D
authors.lastname: Ackerman
authors.forename: Muhammed M
authors.initials: MM
authors.lastname: Alam
authors.forename: Micha B A
authors.initials: MB
authors.lastname: Kunze
authors.forename: Christopher W M
authors.initials: CW
authors.lastname: Kay
authors.forename: David
authors.initials: D
authors.lastname: Gems
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D005293:Ferritins / Q000096:biosynthesis; D007501:Iron / Q000494:pharmacology / Q000502:physiology*; D008136:Longevity / Q000187:drug effects / Q000235:genetics; D009154:Mutation; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D017262:Siderophores / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D029742:Caenorhabditis elegans Proteins; D017262:Siderophores; D005293:Ferritins; D020122:tert-Butylhydroperoxide; D007501:Iron; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D003676:Deferoxamine