title: Evolutionary conservation of regulated longevity assurance mechanisms.
abstract: BACKGROUND
  To what extent are the determinants of aging in animal species universal? Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is an evolutionarily conserved (public) regulator of longevity; yet it remains unclear whether the genes and biochemical processes through which IIS acts on aging are public or private (that is, lineage specific). To address this, we have applied a novel, multi-level cross-species comparative analysis to compare gene expression changes accompanying increased longevity in mutant nematodes, fruitflies and mice with reduced IIS.
  
  
  RESULTS
  Surprisingly, there is little evolutionary conservation at the level of individual, orthologous genes or paralogous genes under IIS regulation. However, a number of gene categories are significantly enriched for genes whose expression changes in long-lived animals of all three species. Down-regulated categories include protein biosynthesis-associated genes. Up-regulated categories include sugar catabolism, energy generation, glutathione-S-transferases (GSTs) and several other categories linked to cellular detoxification (that is, phase 1 and phase 2 metabolism of xenobiotic and endobiotic toxins). Protein biosynthesis and GST activity have recently been linked to aging and longevity assurance, respectively.
  
  
  CONCLUSIONS
  These processes represent candidate, regulated mechanisms of longevity-control that are conserved across animal species. The longevity assurance mechanisms via which IIS acts appear to be lineage-specific at the gene level (private), but conserved at the process level (or semi-public). In the case of GSTs, and cellular detoxification generally, this suggests that the mechanisms of aging against which longevity assurance mechanisms act are, to some extent, lineage specific.
authors.affiliation: Department of Biology, University College London, London WC1E 6BT, UK. josh.mcelwee@gmail.com
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: McElwee
authors.forename: Eugene
authors.initials: E
authors.lastname: Schuster
authors.forename: Eric
authors.initials: E
authors.lastname: Blanc
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Piper
authors.forename: James H
authors.initials: JH
authors.lastname: Thomas
authors.forename: Dhaval S
authors.initials: DS
authors.lastname: Patel
authors.forename: Colin
authors.initials: C
authors.lastname: Selman
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Withers
authors.forename: Janet M
authors.initials: JM
authors.lastname: Thornton
authors.forename: Linda
authors.initials: L
authors.lastname: Partridge
authors.forename: David
authors.initials: D
authors.lastname: Gems
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005982:Glutathione Transferase / Q000235:genetics; D007328:Insulin / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D051379:Mice; D014176:Protein Biosynthesis / Q000235:genetics; D015398:Signal Transduction
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D005982:Glutathione Transferase