Manipulation of in vivo iron levels can alter resistance to oxidative stress without affecting ageing in the nematode C. elegans

Publication date: May 2012 Source:Mechanisms of Ageing and Development, Volume 133, Issue 5 Author(s): Sara Valentini , Filipe Cabreiro , Daniel Ackerman , Muhammed M. Alam , Micha B.A. Kunze , Christopher W.M. Kay , David Gems 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 9mM Fe(III) or greater, but 15mM 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 ...

Source: Mechanisms of Ageing and Development - November 7, 2014 Category: Geriatrics Source Type: research