An Example of Phospholipid and Lifespan Data
One of the lines of evidence that points to mitochondrial damage as an important contribution to degenerative aging is that the life spans of mammalian species correlate well with varying composition of mitochondrial membranes. Differences in composition produce membranes that have more or less resistance to oxidative damage, such as that caused as a side-effect of the processes taking place inside mitochondria when they generate energy store molecules to power other cellular mechanisms. The membrane pacemaker theory of aging is associated with these details.
Learning more about membrane composition and the fine details of how it interacts with damage processes will not tell us how to fix mitochondrial damage and thus greatly improve matters in aging by reversing its course, however. That is already known: the biotechnologies needed to repair mitochondria or work around the damage are established visions, under development in a preliminary fashion, and emerging from entirely separate fields of research. What we should take away from the work linked here is a sense that there are multiple areas of evidence to suggest that repairing damaged mitochondria throughout the body will be of significant benefit, a form of rejuvenation, and thus worthy of greater investment.
The maximal lifespan (MLS) of mammals is inversely correlated with the peroxidation index, a measure of the proportion and level of unsaturation of polyunsaturated fatty acids (PUFA) in membranes. This relationship is likely related to the fact that PUFA are highly susceptible to damage by peroxidation. Previous comparative work has examined membrane composition at the level of fatty acids, and relatively little is known regarding the distribution of PUFA across phospholipid classes or phospholipid molecules. In addition, data for humans is extremely rare in this area.Here we present the first shotgun lipidomics analysis of mitochondrial membranes and the peroxidation index of skeletal muscle, liver, and brain in three mammals that span the range of mammalian longevity. The species compared were mice (MLS of 4 years), pigs (MLS of 27 years), and humans (MLS of 122 years). Mouse mitochondria contained highly unsaturated PUFA in all phospholipid classes. Human mitochondria had lower PUFA content and a lower degree of unsaturation of PUFA. Pig mitochondria shared characteristics of both mice and humans. We found that membrane susceptibility to peroxidation was primarily determined by a limited number of phospholipid molecules that differed between both tissues and species.