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

Whole genome sequences of 2 octogenarians with sustained cognitive abilities.

Author information

1
Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
2
Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
3
Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA. Electronic address: JKramer@Memory.ucsf.edu.
4
Department of Neurology, University of California San Francisco, San Francisco, CA, USA. Electronic address: jorge.oksenberg@ucsf.edu.

Abstract

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

[Indexed for MEDLINE]
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