Genetic Signatures of Exceptional Longevity in Humans

ArticleinScience 2010 · July 2010with10 Reads
Impact Factor: 33.61 · DOI: 10.1126/science.1190532 · Source: PubMed


    Healthy aging is thought to reflect the combined influence of environmental factors (lifestyle choices) and genetic factors.
    To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity (EL) in 1055 centenarians
    and 1267 controls. Using these data, we built a genetic model that includes 150 single-nucleotide polymorphisms (SNPs) and
    found that it could predict EL with 77% accuracy in an independent set of centenarians and controls. Further in silico analysis
    revealed that 90% of centenarians can be grouped into 19 clusters characterized by different combinations of SNP genotypes—or
    genetic signatures—of varying predictive value. The different signatures, which attest to the genetic complexity of EL, correlated
    with differences in the prevalence and age of onset of age-associated diseases (e.g., dementia, hypertension, and cardiovascular
    disease) and may help dissect this complex phenotype into subphenotypes of healthy aging.