A mitochondrial haplogroup is associated with decreased longevity in a historic new world population.

Interest in mitochondrial influences on extended longevity has been mounting, as evidenced by a growing literature. Such work has demonstrated that some haplogroups are associated with increased longevity and that such associations are population specific. Most previous work, however, suffers from the methodological shortcoming that long-lived individuals are compared with "controls" who are born decades after the aged individuals. The only true controls of the elderly are people who were born in the same time period but who did not have extended longevity. Here we present results of a study in which we are able to test whether longevity is independent of haplogroup type, controlling for time period, by using mtDNA genealogies. Since mtDNA does not recombine, we know the mtDNA haplogroup of the maternal ancestors of our living participants. Thus, we can compare the haplogroup of people with and without extended longevity who were born during the same time period. Our sample is an admixed New World population that has haplogroups of Amerindian, European, and African origin. We show that women who belong to Amerindian, European, and African haplogroups do not differ in their mean longevity. Therefore, to the extent that ethnicity was tied in this population to mtDNA make-up, such ethnicity did not impact longevity. In support of previous suggestions that the link between mtDNA haplogroups and longevity is specific to the population being studied, we found an association between haplogroup C and decreased longevity. Interestingly, the lifetime reproductive success and the number of grandchildren produced via a daughter of women with haplogroup C are not reduced. Our diachronic approach to the mtDNA and longevity link allowed us to determine that the same haplogroup is associated with decreased longevity during different time periods and allowed us to compare the haplogroup of short- and long-lived individuals born during the same time period. By controlling for time period, we minimized the effect of different cultural and ecological environments on differential longevity. With our diachronic approach, we investigated the mtDNA and longevity link with a biocultural perspective.

High mitochondrial mutation rates estimated from deep-rooting Costa Rican pedigrees.

Estimates of mutation rates for the noncoding hypervariable Region I (HVR-I) of mitochondrial DNA vary widely, depending on whether they are inferred from phylogenies (assuming that molecular evolution is clock-like) or directly from pedigrees. All pedigree-based studies so far were conducted on populations of European origin. In this article, we analyzed 19 deep-rooting pedigrees in a population of mixed origin in Costa Rica. We calculated two estimates of the HVR-I mutation rate, one considering all apparent mutations, and one disregarding changes at sites known to be mutational hot spots and eliminating genealogy branches which might be suspected to include errors, or unrecognized adoptions along the female lines. At the end of this procedure, we still observed a mutation rate equal to 1.24 × 10(-6) , per site per year, i.e., at least threefold as high as estimates derived from phylogenies. Our results confirm that mutation rates observed in pedigrees are much higher than estimated assuming a neutral model of long-term HVRI evolution. We argue that until the cause of these discrepancies will be fully understood, both lower estimates (i.e., those derived from phylogenetic comparisons) and higher, direct estimates such as those obtained in this study, should be considered when modeling evolutionary and demographic processes.

Mitochondrial polymorphisms associated with differential longevity do not impact lifetime-reproductive success.

OBJECTIVE: To determine if individuals who carry mitochondrial markers which have been previously shown to affect longevity also have differential lifetime reproductive success (LRS). METHODS: We extracted the mtDNA from living subjects residing in Atenas, Costa Rica. Since mtDNA does not recombine, and its probability of mutation is low, we assume that all maternal ancestors of the living subjects have the same mtDNA. We reconstructed the maternal genealogy of the living subjects, so that we have information on the LRS and longevity of the maternal ancestors of the living subjects. We compared the LRS of women who carried the 5178A marker in haplogroup D (associated with decreased longevity) and who carried the 150T polymorphism (associated with increased longevity) with the LRS of controls born in the same half century time period from 1750 to 1939. RESULTS: We found that the LRS of neither group of women with a longevity-associated polymorphism (LAP) differed from the LRS of controls, even if these women differed significantly from the controls in their longevity. CONCLUSIONS: Although LAPS significantly affect longevity, such differential longevity does not result in differential lifetime reproductive success. From an evolutionary perspective, these longevity-associated polymorphisms do not affect the carriers' Darwinian fitness.

Mitochondrial polymorphisms are associated both with increased and decreased longevity.

Previous work compared frequency of longevity-associated polymorphisms (LAPS) in long-lived individuals and in controls from the general population (primarily in Europe and Japan), suggesting the polymorphisms are responsible for unusual longevity. However, individuals from the general population are not the control group for long-lived subjects because both were born in different periods. We report results of a project which collected mtDNA from living subjects in Costa Rica, and traced back their maternal genealogy. Since mtDNA does not recombine and its probability of mutation is low, we can assume that the maternal ancestors had the same mtDNA of their descendants. We compared the longevity of individuals with LAPS with the longevity of controls born in the same time period. We did not confirm previous associations for several markers, but found that the 5178A mutation in haplogroup D is associated with decreased longevity, whereas the 150T mutation is associated with increased longevity. These associations however, are not significant for all time periods under study. While our data confirm that mtDNA make up affects longevity, they also indicate that the time period in which a person was born had a much greater impact on longevity than presence or absence of a marker.