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Life extending mild heat stress induce long-term changes in metabolites associated with energy metabolism in male Drosophila melanogaster
Poster Title: Life extending mild heat stress induce long-term changes in metabolites associated with energy metabolism in male Drosophila melanogaster
Submitted on 30 Jun 2015
Author(s): Pernille Sarup, Volker Loeschcke, Anders Malmendal
Affiliations: Centre for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University (DK). 2 Department of Bioscience, Aarhus University (DK). 3 Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen (DK).
This poster was presented at 2015 Metabolomics Conference
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Poster Information
Abstract: Short bouts of mild stress early in life can affect many life-history-traits at later life-stages. Depending on the severity of the stress and the state of the individual experiencing the stress, the late-acting effects might be beneficial or detrimental. The beneficial effects probably occur when stressful conditions induce maintenance and repair pathways to an extent that exceeds the damage that the stress has caused. This is termed hormesis and among other effects it can result in increased general stress resistance and lifespan. As of yet little is known about the exact mechanisms underlying hormesis.
We used NMR spectroscopy to investigate the long-term effects of repeated mild heat treatments (day three, six, and nine), previously shown to increase lifespan, on the metabolome of Drosophila melanogaster from 3 genetically independent lines. Five replicates of samples consisting of 50 males each were taken before heat treatment and from untreated (L) and treated (H) flies at day 19 and
35. Principal component analysis (PCA) was carried out on the full data using Simca 13.0. The number of significant PCs was assessed by leave one out cross validation. Metabolites affected by the hormesis treatment were identified using t-tests between H and L spectra at 19 or 35 days of age.
The metabolome of the heat-treated flies is clearly distinguishable from control flies 10 days after the last bout of stress. 40% higher levels of alanine and lactate were measured. Glucose was also higher and glutamate lower, both by 10%. However, 26 days after the last bout of mild stress, no general effect of the heat treatments could be detected in the metabolome. The metabolite changes induced at day 19 by the hormetic treatment are indicative of a shift in the energy metabolism. Glucose is metabolized to pyruvate, which in turn can be transformed to acetyl CoA, lactate and alanine. Acetyl- CoA is synthesized by the pyruvate dehydrogenase complex and is usually further metabolized in the TCA cycle or used for fatty acid synthesis. Lactate is synthesized by lactate dehydrogenase in the cori cycle, and alanine by alanine transaminase in the alanine cycle using glutamate for the transamination. Glucose is regenerated from alanine and lactate in the fat body. Thus, to obtain the observed changes either the glucose intake has been increased, the need for acetyl-CoA is smaller, or there is a change in regulation of the energy metabolism. Metabolic reprogramming has previously been associated with the life extending effects of dietary restriction.
The metabolite changes indicated a change in energy metabolism, suggesting that hormesis is not only due to induced repair pathways.
Summary: Mild heat stress early in life can extend lifespan. The mechanism behind this effect is unknown, but induced repair pathways has been suggested. We investigated using NMR spectroscopy.The metabolite changes indicates a shift in energy metabolism induced by heat treatment. Metabolic reprogramming is associated with the life extending effects of dietary restriction. The mechanisms behind heat stress induced increase in lifespan might might not be limited to induced repair pathways.References: Sørensen et al. 2007 Exp Gerontol. 42: 1123–1129; Sarup et al. 2014 Exp Gerontol.50: 34–39 Masoro 2005 Mechanisms of Ageing and Development. 126: 913–922Report abuse »
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