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Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage

Cabreiro, F; Ackerman, D; Doonan, R; Araiz, C; Back, P; Papp, D; Braeckman, BP; (2011) Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radical Biology and Medicine , 51 (8) 1575 - 1582. 10.1016/j.freeradbiomed.2011.07.020. Gold open access

Abstract

The superoxide free radical (O-2(center dot-)) has been viewed as a likely major contributor to aging. If this is correct, then superoxide dismutase (SOD), which removes O-2(center dot-), should contribute to longevity assurance. In Caenorhabditis elegans, overexpression (OE) of the major cytosolic Cu/Zn-SOD, sod-1, increases life span. But is this increase caused by enhanced antioxidant defense? sod-1 OE did not reduce measures of lipid oxidation or glycation and actually increased levels of protein oxidation. The effect of sod-1 OE on life span was dependent on the DAF-16/FoxO transcription factor (TF) and, partially, on the heat shock TF HSF-1. Similarly, overexpression of sod-2 (major mitochondrial Mn-SOD) resulted in life-span extension that was daf-16 dependent. sod-1 OE increased steady-state hydrogen peroxide (H2O2) levels in vivo. However, co-overexpression of catalase did not suppress the life-span extension, arguing against H2O2 as a cause of longevity. sod-1 OE increased hsp-4 expression, suggesting increased endoplasmic reticulum (ER) stress. Moreover, longevity was partially suppressed by inactivation of ire-1 and xbp-1, mediators of the ER stress response. This suggests that high levels of SOD-1 protein may challenge protein-folding homeostasis, triggering a daf-16- and hsf-1-dependent stress response that extends life span. These findings imply that SOD overexpression increases C. elegans life span, not by removal of O-2(center dot-), but instead by activating longevity-promoting transcription factors. (C) 2011 Elsevier Inc. All rights reserved.

Type: Article
Title: Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage
Open access status: An open access publication
DOI: 10.1016/j.freeradbiomed.2011.07.020
Publisher version: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC32026...
Language: English
Keywords: Aging, Caenorhabditis elegans, daf-16/FoxO, ER stress, Oxidative damage, Superoxide dismutase, Free radicals, STRESS RESISTANCE, ROS-GENERATOR, C. ELEGANS, LONGEVITY, MUTANTS, EXPRESSION, HORMESIS, TISSUE, EXTENSION, DAF-16
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1323112
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