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Evolutionary conservation of regulated longevity assurance mechanisms

McElwee, JJ; Schuster, E; Blanc, E; Piper, MD; Thomas, JH; Patel, DS; Selman, C; ... Gems, D; + view all (2007) Evolutionary conservation of regulated longevity assurance mechanisms. GENOME BIOL , 8 (7) , Article R132. 10.1186/gb-2007-8-7-r132. Green open access

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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 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.

Type: Article
Title: Evolutionary conservation of regulated longevity assurance mechanisms
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/gb-2007-8-7-r132
Publisher version: http://dx.doi.org/10.1186/gb-2007-8-7-r132
Language: English
Additional information: © 2007 McElwee et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: LIFE-SPAN EXTENSION, AMES DWARF MICE, NEMATODE CAENORHABDITIS-ELEGANS, MULTIPLE SEQUENCE ALIGNMENT, GENE-EXPRESSION PROFILE, LIVED DAF-2 MUTANTS, C-ELEGANS, GLUTATHIONE TRANSFERASES, INSULIN-RECEPTOR, DROSOPHILA-MELANOGASTER
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10437
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