Evolutionary conservation of regulated longevity assurance mechanisms.
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.
McElwee
Joshua J
JJ
Department of Biology, University College London, London WC1E 6BT, UK. josh.mcelwee@gmail.com
Schuster
Eugene
E
Blanc
Eric
E
Piper
Matthew D
MD
Thomas
James H
JH
Patel
Dhaval S
DS
Selman
Colin
C
Withers
Dominic J
DJ
Thornton
Janet M
JM
Partridge
Linda
L
Gems
David
D
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
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D005982:Glutathione Transferase