Characterization of Deleterious Variation in Centenarian Genomes
2013 new Scholar Award in aging
In the United States, only about one person in 5,000 achieves an age of 100 years or more. Demographers and epidemiologists have estimated that the length of human lifespan is a moderately heritable trait, with the offspring of individuals achieving old age being more likely to also achieve old age themselves. In addition, the extreme old ages associated with centenarians appear to run in families, with siblings of centenarians having a much greater chance of also attaining the age of 100. Therefore, while non-genetic factors including diet and physical activity are clearly very important in determining human longevity, it appears that there is also a significant genetic component in the determination of lifespan. However, due to the complexity of studying aging in humans, the genetics of human aging have remained largely unknown. In recent years, the increasing availability of high-throughput DNA sequencing technologies has allowed us to investigate the genomes of large numbers of individuals for the first time. Using these technologies, it has become clear that most of us have ‘imperfect’ genomes that contain a number of rare genetic variants that appear to abolish the function of a gene, despite no obvious evidence of ill health. One possibility is that the role of these variants is masked at young ages, but become more apparent later in life. As such, we hypothesize that individuals achieving extreme old age have fewer of these deleterious variants in their genomes, and this in turn contributes to their long lifespans. With this idea in mind, the objective of our research is to study the genomes of centenarian individuals and compare them to individuals with typical lifespans. In doing so, we hope to be able to better understand the genomic characteristics associated with longevity.