Lipid peroxidation and animal longevity
Ageing is universal among animals and different animal species have distinctive maximum lifespans. This variation in longevity achieved by evolution is several orders-of-magnitude greater than that achieved by experimental or genetic manipulation and can provide considerable insight into the mechanisms of ageing. Following the observation that membrane fatty acid composition varies with body size among mammal species, it became apparent that the fatty acid composition of membrane lipids was also strongly correlated with the maximum lifespan of mammals. This emphasised the importance of lipid peroxidation in ageing and determination of longevity. While saturated and monounsaturated fatty acids are resistant to lipid peroxidation, polyunsaturated fatty acids are peroxidised and the more polyunsaturated the fatty acid the more susceptible it is to peroxidation. It is possible to calculate a peroxidation index (PI) for a particular membrane fatty acid composition and this PI value expresses the calculated susceptibility of the membrane to peroxidative damage as well as the relative abundance of secondary lipid-based reactive species produced by the primary ROS made from mitochondrial respiration. The PI value of membranes is inversely related to lifespan of mammals. Furthermore, exceptionally long-living mammal species (naked mole rats, echidnas and humans) have membrane lipid PI values lower-than-expected for their body size but as expected for their specific lifespan. Similarly, within a mammal species (mice) longliving strains have membrane lipids with a low PI. The experimental treatment of calorierestriction, known to extend lifespan of mammals, has also been shown to decrease membrane PI values. Birds are longer-living than similar-sized mammals and show the same relationship between membrane composition and longevity. An inverse relationship between membrane lipid PI and longevity is also observed in invertebrates, although it is not the same precise relationship as observed in mammals and birds. Experiments to test the link between maximum longevity and membrane composition via diet manipulation have been generally unsuccessful because membrane PI appears to be homeostatically regulated with respect to diet PI. Other recent experimental alterations of membrane composition (e.g., by RNAi knock-down in C. elegans) support a link between membrane fatty acid composition, resistance to oxidative stress and longevity. Other aspects of membrane lipid composition (e.g., plasmalogens and non-methylene-interrupted fatty acids) may also be important for some species. These observations suggest lipid peroxidation is central to the biology of ageing and the determination of the distinctive longevities of different animals.