Investigating a Longevity-Related Mitochondrial Polymorphism

Mitochondrial function is important in determining life span, and mitochondrial damage is one of the root causes of aging. Thus life span differences between similar species may to a large degree reflect differences in the damage resistance of mitochondria, and a number of studies in recent years have shown that some human mitochondrial haplogroups - which represent characteristic variations in mitochondrial DNA - can be correlated with increased longevity.

The way in which mitochondria become damaged involves the production of reactive oxygen species (ROS) in the course of generating fuel to power the cell that contains them. Here researchers show that a longevity-associated difference in mitochondrial DNA reduces the pace of ROS production - which fits nicely with the present understanding of the role of mitochondria in aging:

Mitochondrial DNA (mtDNA) is highly polymorphic, and its variations in humans may contribute to individual differences in function. [Researchers] found a strikingly higher frequency of a C150T transition in the D-loop of mtDNA from centenarians and twins of an Italian population.

The C150T transition is a polymorphism associated with several haplogroups. To determine whether haplogroups that carry the C150T transition display any phenotype that may be advantageous for longevity, we analyzed cybrids carrying or not the C150T transition. These cybrids were obtained by fusing cytoplasts derived from human fibroblasts with human mtDNA-less cells.

We have found no association of respiratory capacity, mtDNA level, mitochondrial gene expression level, or growth rate with the presence of the C150T transition. However, we have found that the cybrids with haplogroups that include the C150T transition have in common a lower reactive oxygen species (ROS) production rate than the haplogroup-matched cybrids without that transition. Thus, the lower ROS production rate may be a factor in the increased longevity associated with [these] haplogroups.

Link: http://dx.doi.org/10.1371/journal.pone.0046473