Antioxidant enzyme activities are not broadly correlated with longevity in 14 vertebrate endotherm species.
ABSTRACT The free radical theory of ageing posits that accrual of oxidative damage underlies the increased cellular, tissue and organ dysfunction and failure associated with advanced age. In support of this theory, cellular resistance to oxidative stress is highly correlated with life span, suggesting that prevention or repair of oxidative damage might indeed be essential for longevity. To test the hypothesis that the prevention of oxidative damage underlies longevity, we measured the activities of the five major intracellular antioxidant enzymes in brain, heart and liver tissue of 14 mammalian and avian species with maximum life spans (MLSPs) ranging from 3 years to over 100 years. Our data set included Snell dwarf mice in which life span is increased by approximately 50% compared to their normal littermates. We found that CuZn superoxide dismutase, the major cytosolic superoxide dismutase, showed no correlation with MLSP in any of the three organs. Similarly, neither glutathione peroxidase nor glutathione reductase activities correlated with MLSP. MnSOD, the sole mitochondrial superoxide dismutase in mammals and birds, was positively correlated with MLSP only for brain tissue. This same trend was observed for catalase. For all correlational data, effects of body mass and phylogenetic relatedness were removed using residual analysis and Felsenstein's phylogenetically independent contrasts. Our results are not consistent with a causal role for intracellular antioxidant enzymes in longevity, similar to recent reports from studies utilising genetic modifications of mice (Pérez et al., Biochim Biophys Acta 1790:1005-1014, 2009). However, our results indicate a specific augmentation of reactive oxygen species neutralising activities in brain associated with longevity.
[show abstract] [hide abstract]
ABSTRACT: As alterations of the redox homeostasis lie at the root of many pathophysiological processes in human health, redox proteomics holds the promise to shed further light on fundamental biological processes. In this review, the mechanisms of reactive oxygen species (ROS) and reactive nitrogen species (RNS) production are reviewed, mainly addressing those chemical phenomena which have already been associated with pathological conditions (of the central nervous system, cardiovascular system, or simply related to aging and altered-cell cycle regulation). From Alzheimer's to Parkinson's and Hungtinton's disease, from ageing to cancer, oxidative stress (OS) appears to represent a common trait in so many relevant biological aspects of human health, that further investments in the field of redox proteomics ought to be mandatory. For the foreseeable future, redox proteomics will likely play a pivotal role in the quest for new therapeutical targets and their validation, in the process of determining OS-triggered cellular alteration upon drug treatments and thus in the very heart of the design and testing of new drugs and their metabolites against those pathologies relying on altered redox homeostasis.Journal of proteomics 01/2011; 74(12):2575-95. · 5.07 Impact Factor