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Evolutionary conservation of regulated longevity assurance mechanisms

Show simple item record McElwee, Joshua J. en_US Schuster, Eugene en_US Blanc, Eric en_US Piper, Matthew D. en_US Thomas, James H. en_US Patel, Dhaval S. en_US Selman, Colin en_US Withers, Dominic J. en_US Thorton, Janet M. en_US Partridge, Linda en_US Gems, David en_US 2010-05-06T20:07:30Z 2010-05-06T20:07:30Z 2007 en_US
dc.identifier.citation McElwee J, Schuster E, Blanc E, et al. Evolutionary conservation of regulated longevity assurance mechanisms. Genome Biology. 2007;8(7):R132. en_US
dc.identifier.other 10.1186/gb-2007-8-7-r132 en_US
dc.identifier.uri en_US
dc.description.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. 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. en_US
dc.description.sponsorship Supported by a grant from the Wellcome Trust to EB, DG, JJM, DSP, LP, MP, CS, ES, JMT and DJW, and the Biotechnology and Biological Sciences Research Council to LP. en_US
dc.language.iso en_US en_US
dc.title Evolutionary conservation of regulated longevity assurance mechanisms en_US
dc.type Article en_US

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