title: Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-1340, USA. ccurtis@usc.edu
authors: Christina
authors: C
authors: Curtis
authors: Gary N
authors: GN
authors: Landis
authors: Donna
authors: D
authors: Folk
authors: Nancy B
authors: NB
authors: Wehr
authors: Nicholas
authors: N
authors: Hoe
authors: Morris
authors: M
authors: Waskar
authors: Diana
authors: D
authors: Abdueva
authors: Dmitriy
authors: D
authors: Skvortsov
authors: Daniel
authors: D
authors: Ford
authors: Allan
authors: A
authors: Luu
authors: Ananth
authors: A
authors: Badrinath
authors: Rodney L
authors: RL
authors: Levine
authors: Timothy J
authors: TJ
authors: Bradley
authors: Simon
authors: S
authors: Tavaré
authors: John
authors: J
authors: Tower
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D050260:Carbohydrate Metabolism; D004331:Drosophila melanogaster / Q000502:physiology*; D004579:Electron Transport; D005260:Female; D020869:Gene Expression Profiling; D008136:Longevity; D008297:Male; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*
chemical_list: D013482:Superoxide Dismutase