APOE Alleles and extreme human longevity

Paola Sebastiani, Anastasia Gurinovich, Marianne Nygaard, Takashi Sasaki, Benjamin Sweigart, Harold Bae, Stacy L. Andersen, Francesco Villa, Gil Atzmon, Kaare Christensen, Yasumichi Arai, Nir Barzilai, Annibale Puca, Lene Christiansen, Nobuyoshi Hirose, Thomas T. Perls

Research output: Contribution to journalArticlepeer-review

Abstract

We assembled a collection of 28,297 participants from seven studies of longevity and healthy aging comprising New England Centenarian, Long Life Family, Longevity Gene Population, Southern Italian Centenarian, Japanese Centenarian, the Danish Longevity, and the Health and Retirement Studies to investigate the association between the APOE alleles ϵ 2 ϵ 3 and ϵ 4 and extreme human longevity and age at death. By using three different genetic models and two definitions of extreme longevity based on either a threshold model or age at death, we show that ϵ 4 is associated with a substantially decreased odds for extreme longevity, and increased risk for death that persists even beyond ages reached by less than 1% of the population. We also show that carrying the ϵ 2 ϵ 2 or ϵ 2 ϵ 3 genotype is associated with significantly increased odds to reach extreme longevity, with decreased risk for death compared with carrying the genotype ϵ 3 ϵ 3 but with only a modest reduction in risk for death beyond an age reached by less than 1% of the population.

Original languageEnglish
Pages (from-to)44-51
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume74
Issue number1
DOIs
StatePublished - 1 Jan 2019

Bibliographical note

Funding Information:
This work was supported by the National Institute on Aging (NIA cooperative agreements U01-AG023755 TP, U19-AG023122 TP, and R21AG056630 PS), the National Institute of General Medical Sciences (NIGMS) Interdisciplinary Training Grant for Biostatisticians Program (T32 GM74905), the William M. Wood Foundation (T.T.P.), and the Paulette and Marty Samowitz Family Foundation (T.T.P.). The Health and Retirement Study genetic data is sponsored by the NIA (grant numbers U01AG009740, RC2AG036495, and RC4AG039029) and was conducted by the University of Michigan.The Nathan Shock Centers of Excellence in the Basic Biology of Aging (P30AG038072) (N.B.), the Glenn Center for the Biology of Aging (Paul Glenn Foundation for Medical Research) (N.B.), NIH/NIA 1 R01AG044829 (PIs-Veghese/Barzilai), NIH/NIA1 R01 AG 042188-01 (Atzmon/Barzilai, NIH-1 R01 AG 046949 - 01 (Barzilai, PI). The Danish Twin Registry is supported by the Danish Agency for Science, Technology and Innovation, and the US National Institutes of Health (P01 AG08761). The Danish Aging Research Center is supported by the Velux Foundation. The Japanese Centenarian Study was supported by AMED Program for an Integrated Database of Clinical and Genomic Information, and Program for Initiative Research Projects, Keio University. Genotyping of APOE in the New England Centenarian Study was supported by the Clinical and Translational Science Institute, Boston University (1UL1TR001430).

Publisher Copyright:
© 2018 The Author(s). Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

Keywords

  • APOE
  • Extreme human longevity
  • Genetic association
  • Survival distribution

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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