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. © 2012 Elsevier Ireland Ltd.