title: Whole genome sequences of 2 octogenarians with sustained cognitive abilities.
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.
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Nickles
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Lohith
authors.initials: L
authors.lastname: Madireddy
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Nihar
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Noriko
authors.initials: N
authors.lastname: Isobe
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Baranzini
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA. Electronic address: JKramer@Memory.ucsf.edu.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, CA, USA. Electronic address: jorge.oksenberg@ucsf.edu.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000523:psychology*; D053327:Apolipoprotein E4 / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D005260:Female; D005807:Genes, Overlapping; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D008136:Longevity / Q000235:genetics; D057285:Precision Medicine
chemical_list: D053327:Apolipoprotein E4
keywords: APOEε4; Aging; Cognition; Genetics; Next generation sequencing; Personalized medicine