Inheritance of unusual longevity: a diachronic study

University Of South Florida, Tampa FL

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Abstract

This proposal responds to Research objective #18, Exceptional Human Lon,qevity, of the NIA pilot research grant program. We propose an innovative approach to the study of exceptional human longevity by comparing the mean longevity of all mtDNA haplotypes found in a New World population. We propose to compare the mean longevity of pedigrees with different haplotypes, by comparing individuals born on the same birth cohort, whether they lived to be old or not. In this manner we will advance the work already done in cross-sectional studies, which could not compare individuals of unusual longevity with controls born on the same cohort. A necessary assumption of this study is that the mtDNA haplotypes have been transmitted without mutating. Although it is unlikely that this assumption will be violated, we will estimate for each pedigree the probability that no mutation has occurred along the meioses considered, using a coalescent-based approach. For each subject whose mtDNA we collect, we will determine: 1. Age of mother at her death or age at time of interview 2. Number of siblings of subject and age at death or age at time of interview 3. Age of mother's mother at her death or age at time of interview 4. Number of siblings of mother, and age at death or at the time of the interview, and so on. This information will be entered by genealogy and by birth cohort (defined by 50 year periods). In this manner we will be able to access the age at death of all the subjects by birth cohort and by genealogy. The study will take place in a small, socio-economically homogeneous community, where economic differences are not likely to account for differential longevity. The project benefits from a group of researchers (anthropologists, population geneticists, genealogists) who have the expertise to face the interdisciplinary challenges that this subject will present, as well as from excellent field conditions. We also discuss how this pilot study could produce an R01 research project grant.