Identification of amino acids in mitochondrially encoded proteins that correlate with lifespan

Animals show a huge diversity in their lifespan that can vary from a few weeks to over a hundred years in vertebrates. Size is a key element in this variation and the positive correlation between size and maximum lifespan can be observed in each class of vertebrate. Some groups and species clearly stand out in this size-lifespan relationship and the ones with exceptionally long lifespan have been studied to understand the biological causes of their low aging rate. Among the potential explanations of animals' lifespan variations, mitochondria and mitochondrially encoded genes have drawn attention because of their importance in the aging process. To understand both the extent of lifespan variations and their dependence to genes and amino acid variations in mitochondrial genes and DNA (mtDNA), we analyze in a systematic way all 13 proteins encoded by mitochondria in all vertebrates for which we had information on weight, maximum lifespan and mtDNA sequence. This comparison allows us to visualize positions, and even specific amino acids, in these sequences that correlate with lifespan. With this approach, we draw a map of 356 amino acid residues, at 296 positions within the sequence, that correlate with longer or shorter lifespan. We also compared this map with the human mitochondrial polymorphism to determine its potential as a predictive tool.