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Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes

Christina Curtis1, Gary N Landis1, Donna Folk2, Nancy B Wehr3, Nicholas Hoe1, Morris Waskar1, Diana Abdueva14, Dmitriy Skvortsov1, Daniel Ford1, Allan Luu1, Ananth Badrinath1, Rodney L Levine3, Timothy J Bradley2, Simon Tavaré15 and John Tower1*

Author Affiliations

1 Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-1340, USA

2 Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92717, USA

3 Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, MD 20817-6735, USA

4 Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9034, USA

5 Department of Oncology, University of Cambridge, Cambridge CB2 2XZ, UK

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Genome Biology 2007, 8:R262  doi:10.1186/gb-2007-8-12-r262

Published: 9 December 2007



Several interventions increase lifespan in model organisms, including reduced insulin/insulin-like growth factor-like signaling (IIS), FOXO transcription factor activation, dietary restriction, and superoxide dismutase (SOD) over-expression. One question is whether these manipulations function through different mechanisms, or whether they intersect on common processes affecting aging.


A doxycycline-regulated system was used to over-express manganese-SOD (MnSOD) in adult Drosophila, yielding increases in mean and maximal lifespan of 20%. Increased lifespan resulted from lowered initial mortality rate and required MnSOD over-expression in the adult. Transcriptional profiling indicated that the expression of specific genes was altered by MnSOD in a manner opposite to their pattern during normal aging, revealing a set of candidate biomarkers of aging enriched for carbohydrate metabolism and electron transport genes and suggesting a true delay in physiological aging, rather than a novel phenotype. Strikingly, cross-dataset comparisons indicated that the pattern of gene expression caused by MnSOD was similar to that observed in long-lived Caenorhabditis elegans insulin-like signaling mutants and to the xenobiotic stress response, thus exposing potential conserved longevity promoting genes and implicating detoxification in Drosophila longevity.


The data suggest that MnSOD up-regulation and a retrograde signal of reactive oxygen species from the mitochondria normally function as an intermediate step in the extension of lifespan caused by reduced insulin-like signaling in various species. The results implicate a species-conserved net of coordinated genes that affect the rate of senescence by modulating energetic efficiency, purine biosynthesis, apoptotic pathways, endocrine signals, and the detoxification and excretion of metabolites.