OLDMITO

"Oxidation, Lipids, DNA and Mitochondria"

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'The overarching aim of the project is to establish a cause-effect relationship among the mitochondrial processes related to ageing in fish (mitochondrial membrane composition, lipid metabolism, ROS production, antioxidant activities, mitochondrial DNA expression), which will advance our understanding of these mechanisms in ectotherms in order to develop a vertebrate model of ageing. The project will require a multi-disciplinary approach utilising molecular biology and biochemistry. Techniques include subcellular fractionation to obtain the mitochondrial fraction, lipid analyses including thin-layer chromatography (TLC) and gas-chromatography (GC) for phospholipid and fatty acid analysis, biochemical assays to assess peroxidation processes, and molecular analyses including PCR cloning of mitochondrial electron transport chain (ETC) cDNAs and gene expression studies to determine tissue distribution and effects of aging using quantitative real-time PCR. The host institution will be the Institute of Aquaculture (IoA) at University of Stirling (Scotland, United Kingdom), a dedicated research Institute with an International reputation in research and post-graduate teaching. The work in the proposed project falls within the remit of the Molecular Nutrition Group at the IoA, a world-leading group in fish lipid and fatty acid metabolism, nutrition and molecular biology. The proposed research project fits very well within the objectives of FP7 of the European Community. The project is part of research efforts that impact on human health through addressing the important issue of the establishment of a vertebrate model of ageing, which would shorten the phylogenetic distance respecting model and the human species. However, the project is also highly relevant to Theme 2 (Food, Agriculture and Fisheries, Biotechnology). This project will help us to consider new aspects in the fish farming and to improve the efficiency of Aquaculture activities and fish welfare.'

Introduzione (Teaser)

Mitochondria generate most of the energy in the cell and are involved in cell death and cell cycle control, and are implicated in many diseases. Recent evidence that these tiny powerhouses are linked to ageing is being put to the test.

Descrizione progetto (Article)

There are many theories of ageing that implicate the mitochondrion. Reactive oxygen species (ROS) produced by the organelle cause damage to tissues and possibly mitochondrial DNA (mtDNA) that cannot repair itself like its counterpart in the nucleus. The membrane pacemaker theory speculates that damage to mitochondrial membrane lipids by ROS leads to a chain reaction and widespread oxidative damage. Finally, species with a greater proportion of unsaturated fat in the mitochondrial membrane have a higher metabolic rate and therefore a greater proportion of oxidative stress (OS).

The EU-funded 'Oxidation, lipids, DNA and mitochondria' (OLDMITO) project has investigated the validity of these theories using zebrafish (Danio rerio), a short-lived fish, and rainbow trout (Oncorhynchus mykiss) that lives for up to seven years and more so is considered long-lived. The researchers investigated the lipid content of the mitochondrial membrane and mtDNA damage as possible regulators of ageing and welfare.

OLDMITO results showed that changes in mitochondrial phospholipid (PL) content could be related to ageing, particularly cardiolipin and sphingomyelin. These PLs can cause mitochondrial dysfunction and increase in apoptosis as a result of OS. Furthermore, PLs became more unsaturated and OS level increased in line with the membrane pacemaker theory.

Dietary content also had a marked effect on fatty acid content of PLs, which in turn had a significant impact on mtDNA gene expression. These effects differed with fish age and pointed to the fact that diet lipid content can have an impact on mitochondrial function.

Six scientific papers based on the results of the OLDMITO project have been published in peer-reviewed journals. Data from the project stands to contribute to the establishment of a vertebrate model of ageing. Applications of the research may also include improvements in efficiency in the area of fish farming.