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"Oxidation, Lipids, DNA and Mitochondria"

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Ageing linked to mitochondria

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.

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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.

Keywords

Ageing, mitochondria, oxidative stress, phospholipid, diet lipid content

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