Whole genome sequences of 2 octogenarians with sustained cognitive abilities

Neurobiol Aging. 2015 Mar;36(3):1435-8. doi: 10.1016/j.neurobiolaging.2014.11.003. Epub 2014 Dec 16.


Although numerous genetic variants affecting aging and mortality have been identified, for example, apolipoprotein E ε4, the genetic component influencing cognitive aging has not been fully defined yet. A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of 2 female octogenarians. We provide the repertoire of genomic variants that the 2 octogenarians have in common. We also describe the overlap with the previously reported genomes of 2 supercentenarians—individuals aged ≥110 years. We assessed the genetic disease propensities of the octogenarians and non-aged control genomes and could not find support for the hypothesis that long-lived healthy individuals might exhibit greater genetic fitness than the general population. Furthermore, there is no evidence for an accumulation of previously described variants promoting longevity in the 2 octogenarians. These findings suggest that genetic fitness, as currently defined, is not the sole factor enabling an increased life span. We identified a number of healthy-cognitive-aging candidate genetic loci awaiting confirmation in larger studies.

Keywords: APOEε4; Aging; Cognition; Genetics; Next generation sequencing; Personalized medicine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged, 80 and over
  • Aging / genetics*
  • Aging / psychology*
  • Apolipoprotein E4 / genetics
  • Cognition / physiology*
  • Female
  • Genes, Overlapping
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation
  • Genome, Human / genetics*
  • Genomics*
  • Humans
  • Longevity / genetics
  • Precision Medicine


  • Apolipoprotein E4