Evolutionary conservation of regulated longevity assurance mechanisms
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Date
2007Author
McElwee, Joshua J.
Schuster, Eugene
Blanc, Eric
Piper, Matthew D.
Thomas, James H.
Patel, Dhaval S.
Selman, Colin
Withers, Dominic J.
Thorton, Janet M.
Partridge, Linda
Gems, David
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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.
Conclusion: 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 semipublic). 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.