Mitochondria, the power plants of the cell, bear their own mitochondrial DNA (mtDNA) that is inherited from the mother. There are a range of common variants of human mitochondrial DNA known as haplogroups, and given that mitochondria are important in aging there is an expectation that some of the natural variation in human longevity can be explained via haplogroup differences. Indeed, there is evidence to suggest that some haplogroups are better than others when it comes to life expectancy, all other things being equal.
These effects are not large in the grand scheme of things, however, and as for everything involving the genetics of longevity the underlying mechanisms and relationships are complicated:
To re-examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification, while about 1300 mtDNA molecules (650 ultranonagenarians and an equal number of controls) were completely sequenced.
Sequences, unlike standard haplogroup analysis, made possible to evaluate for the first time the cumulative effects of specific, concomitant mtDNA mutations, including those that per se have a low, or very low, impact. In particular, the analysis of the mutations occurring in different OXPHOS complex showed a complex scenario with a different mutation burden in 90+ subjects with respect to controls.
These findings suggested that mutations in subunits of the OXPHOS complex I had a beneficial effect on longevity, while the simultaneous presence of mutations in complex I and III (which also occurs in J subhaplogroups involved in LHON) and in complex I and V seemed to be detrimental, likely explaining previous contradictory results. On the whole, our study, which goes beyond haplogroup analysis, suggests that mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mtDNA genes.