Grant: Doctoral Res. Award - Pop. Genetic, Genetic Epidem. and Complex Disease

The aim of this project is to determine whether variation in the human mitochondrial genome contributes to variability in the aging process. Our study population consists of what gerontologists refer to as the "healthy oldest old" from the Metro Vancouver area. These are individuals that have reached the upper limits of the normal human lifespan (>85 years) and have not developed any of the most common complex age-associated diseases (cancer, cardiopulmonary disease, Alzheimer disease or type II diabetes). The study is designed as a case-control genetic association study, and we will be using the most advanced DNA sequencing technology and computational power available to us at the Genome Sciences Centre to uncover genetic factors that contribute to healthy aging in our study population. Mitochondria act as central regulators of multiple cellular processes including intermediary metabolism, calcium signaling, and apoptosis. Mitochondria are also the primary source of reactive oxygen species that damage proteins and lipids, and can cause mutations in DNA. Heritability studies have shown that the heritability of human longevity has a larger maternal component than paternal component. Since the mitochondrial genome is inherited through the maternal side, this is evidence that the mitochondrial genome plays some role in the aging process. Other studies have shown associations between human lifespan and specific variants in the mitochondrial genome. The Genome Sciences Centre at the BC Cancer Agency is home to some of the world's most advanced DNA sequencing equipment, including several illumina Genome Analyzer machines that are capable of producing over 1 billion bases of sequence data in a single run. We will collaborate with a senior biostatistician at the BC Cancer Agency to use the latest non-parametric statistical techniques to model the impact of sequence variation in the mitochondrial genome on the development of the healthy aging phenotype being studied.