title: Superoxide dismutase mimetics elevate superoxide dismutase activity in vivo but do not retard aging in the nematode Caenorhabditis elegans.
abstract: According to the oxidative damage theory a primary cause of aging is the accrual of molecular damage from reactive oxygen species (ROS), particularly superoxide and its derivatives. This predicts that treatments that reduce ROS levels should retard aging. Using the nematode Caenorhabditis elegans, we tested the effects on stress resistance and life span of treatment with EUK-8 and EUK-134, synthetic mimetics of the antioxidant enzyme superoxide dismutase (SOD), which neutralises superoxide. Treatment with SOD mimetics elevated in vivo SOD activity levels, particularly in mitochondria, where up to 5-fold increases in SOD activity were recorded. Treatment with exogenous SOD mimetics did not affect endogenous protein SOD levels. Where life span was reduced by the superoxide generators paraquat and plumbagin, EUK-8 treatment increased life span in a dose-dependent fashion. Yet in the absence of a superoxide generator, treatment with EUK-8 or EUK-134 did not increase life span, even at doses that were optimal for protection against pro-oxidants. Thus, an elevation of SOD activity levels sufficient to increase life span when it is limited by superoxide generators does not retard aging in the absence of superoxide generators. This suggests that C. elegans life span is not normally limited by levels of superoxide and its derivatives.
authors.affiliation: Department of Biology, University College London, WC1E 6BT, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Keaney
authors.forename: Filip
authors.initials: F
authors.lastname: Matthijssens
authors.forename: Martyn
authors.initials: M
authors.lastname: Sharpe
authors.forename: Jacques
authors.initials: J
authors.lastname: Vanfleteren
authors.forename: David
authors.initials: D
authors.lastname: Gems
mesh_terms: D000375:Aging; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology; D032701:Biomimetics; D017173:Caenorhabditis elegans; D003486:Cyanides / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D005029:Ethylenediamines / Q000494:pharmacology; D005609:Free Radicals; D006540:Herbicides / Q000494:pharmacology; D017895:Manganese Compounds / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010101:Oxygen Consumption; D010269:Paraquat / Q000494:pharmacology; D017382:Reactive Oxygen Species; D012459:Salicylates / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D000969:Antinematodal Agents; D003486:Cyanides; C433928:EUK-134; D005029:Ethylenediamines; D005609:Free Radicals; D006540:Herbicides; D017895:Manganese Compounds; D009285:Naphthoquinones; D009942:Organometallic Compounds; D016877:Oxidants; D017382:Reactive Oxygen Species; D012459:Salicylates; D013481:Superoxides; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II); D013482:Superoxide Dismutase; D010269:Paraquat; C014758:plumbagin