Published Online July 1 2010
< Science Express Index
Science DOI: 10.1126/science.1190532
  • Report

Genetic Signatures of Exceptional Longevity in Humans

  1. Paola Sebastiani1,*,
  2. Nadia Solovieff1,
  3. Annibale Puca2,
  4. Stephen W. Hartley1,
  5. Efthymia Melista3,
  6. Stacy Andersen4,
  7. Daniel A. Dworkis3,
  8. Jemma B. Wilk5,
  9. Richard H. Myers5,
  10. Martin H. Steinberg6,
  11. Monty Montano3,
  12. Clinton T. Baldwin6,7 and
  13. Thomas T. Perls4,*
  1. 1Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  2. 2IRCCS Multimedica, Milano, Italy;Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Segrate, 20122, Italy.
  3. 3Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
  4. 4Section of Geriatrics, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA.
  5. 5Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
  6. 6Departments of Medicine and Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA.
  7. 7Center for Human Genetics, Boston University School of Medicine, Boston, MA 02118, USA.
  1. *To whom correspondence should be addressed. E-mail: sebas{at}bu.edu (P.S.); thperls{at}bu.edu (T.H.P.)

Abstract

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.

  • Received for publication 21 December 2009.
  • Accepted for publication 9 June 2010.