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Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue
The fruitfly Drosophila melanogaster is increasingly used as a model organism for studying acute hypoxia tolerance and for studying aging, but the interactions between these two factors are not well known. Here we show that hypoxia tolerance degrades with age in post-hypoxic recovery of whole-body m...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615305/ https://www.ncbi.nlm.nih.gov/pubmed/19096360 http://dx.doi.org/10.1038/msb.2008.71 |
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author | Coquin, Laurence Feala, Jacob D McCulloch, Andrew D Paternostro, Giovanni |
author_facet | Coquin, Laurence Feala, Jacob D McCulloch, Andrew D Paternostro, Giovanni |
author_sort | Coquin, Laurence |
collection | PubMed |
description | The fruitfly Drosophila melanogaster is increasingly used as a model organism for studying acute hypoxia tolerance and for studying aging, but the interactions between these two factors are not well known. Here we show that hypoxia tolerance degrades with age in post-hypoxic recovery of whole-body movement, heart rate and ATP content. We previously used (1)H NMR metabolomics and a constraint-based model of ATP-generating metabolism to discover the end products of hypoxic metabolism in flies and generate hypotheses for the biological mechanisms. We expand the reactions in the model using tissue- and age-specific microarray data from the literature, and then examine metabolomic profiles of thoraxes after 4 h at 0.5% O(2) and after 5 min of recovery in 40- versus 3-day-old flies. Model simulations were constrained to fluxes calculated from these data. Simulations suggest that the decreased ATP production during reoxygenation seen in aging flies can be attributed to reduced recovery of mitochondrial respiration pathways and concomitant overdependence on the acetate production pathway as an energy source. |
format | Text |
id | pubmed-2615305 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-26153052009-01-09 Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue Coquin, Laurence Feala, Jacob D McCulloch, Andrew D Paternostro, Giovanni Mol Syst Biol Article The fruitfly Drosophila melanogaster is increasingly used as a model organism for studying acute hypoxia tolerance and for studying aging, but the interactions between these two factors are not well known. Here we show that hypoxia tolerance degrades with age in post-hypoxic recovery of whole-body movement, heart rate and ATP content. We previously used (1)H NMR metabolomics and a constraint-based model of ATP-generating metabolism to discover the end products of hypoxic metabolism in flies and generate hypotheses for the biological mechanisms. We expand the reactions in the model using tissue- and age-specific microarray data from the literature, and then examine metabolomic profiles of thoraxes after 4 h at 0.5% O(2) and after 5 min of recovery in 40- versus 3-day-old flies. Model simulations were constrained to fluxes calculated from these data. Simulations suggest that the decreased ATP production during reoxygenation seen in aging flies can be attributed to reduced recovery of mitochondrial respiration pathways and concomitant overdependence on the acetate production pathway as an energy source. Nature Publishing Group 2008-12-16 /pmc/articles/PMC2615305/ /pubmed/19096360 http://dx.doi.org/10.1038/msb.2008.71 Text en Copyright © 2008, EMBO and Nature Publishing Group http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution and reproduction in any medium, provided the original author and source are credited. Creation of derivative works is permitted but the resulting work may be distributed only under the same or similar licence to this one. This licence does not permit commercial exploitation without specific permission. |
spellingShingle | Article Coquin, Laurence Feala, Jacob D McCulloch, Andrew D Paternostro, Giovanni Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue |
title | Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue |
title_full | Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue |
title_fullStr | Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue |
title_full_unstemmed | Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue |
title_short | Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue |
title_sort | metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in drosophila muscle tissue |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615305/ https://www.ncbi.nlm.nih.gov/pubmed/19096360 http://dx.doi.org/10.1038/msb.2008.71 |
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