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 journalJournal articleResearchpeer-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
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume74
Issue number1
Pages (from-to)44–51
ISSN1079-5006
DOIs
Publication statusPublished - 1. Jan 2019

Fingerprint

Alleles
Population
New England
Retirement
Genetic Models
Risk Reduction Behavior
Health

Keywords

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

Cite this

Sebastiani, Paola ; Gurinovich, Anastasia ; Nygaard, Marianne ; Sasaki, Takashi ; Sweigart, Benjamin ; Bae, Harold ; Andersen, Stacy L ; Villa, Francesco ; Atzmon, Gil ; Christensen, Kaare ; Arai, Yasumichi ; Barzilai, Nir ; Puca, Annibale ; Christiansen, Lene ; Hirose, Nobuyoshi ; Perls, Thomas T. / APOE Alleles and Extreme Human Longevity. In: The journals of gerontology. Series A, Biological sciences and medical sciences. 2019 ; Vol. 74, No. 1. pp. 44–51.
@article{25bfcddcc78b4ec1b079e55c586dea1e,
title = "APOE Alleles and Extreme Human Longevity",
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.",
keywords = "APOE, Extreme human longevity, Genetic association, Survival distribution",
author = "Paola Sebastiani and Anastasia Gurinovich and Marianne Nygaard and Takashi Sasaki and Benjamin Sweigart and Harold Bae and Andersen, {Stacy L} and Francesco Villa and Gil Atzmon and Kaare Christensen and Yasumichi Arai and Nir Barzilai and Annibale Puca and Lene Christiansen and Nobuyoshi Hirose and Perls, {Thomas T}",
year = "2019",
month = "1",
day = "1",
doi = "10.1093/gerona/gly174",
language = "English",
volume = "74",
pages = "44–51",
journal = "Journals of Gerontology. Series A: Biological Sciences & Medical Sciences",
issn = "1079-5006",
publisher = "Heinemann",
number = "1",

}

Sebastiani, P, Gurinovich, A, Nygaard, M, Sasaki, T, Sweigart, B, Bae, H, Andersen, SL, Villa, F, Atzmon, G, Christensen, K, Arai, Y, Barzilai, N, Puca, A, Christiansen, L, Hirose, N & Perls, TT 2019, 'APOE Alleles and Extreme Human Longevity', The journals of gerontology. Series A, Biological sciences and medical sciences, vol. 74, no. 1, pp. 44–51. https://doi.org/10.1093/gerona/gly174

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

In: The journals of gerontology. Series A, Biological sciences and medical sciences, Vol. 74, No. 1, 01.01.2019, p. 44–51.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - APOE Alleles and Extreme Human Longevity

AU - Sebastiani, Paola

AU - Gurinovich, Anastasia

AU - Nygaard, Marianne

AU - Sasaki, Takashi

AU - Sweigart, Benjamin

AU - Bae, Harold

AU - Andersen, Stacy L

AU - Villa, Francesco

AU - Atzmon, Gil

AU - Christensen, Kaare

AU - Arai, Yasumichi

AU - Barzilai, Nir

AU - Puca, Annibale

AU - Christiansen, Lene

AU - Hirose, Nobuyoshi

AU - Perls, Thomas T

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - APOE

KW - Extreme human longevity

KW - Genetic association

KW - Survival distribution

U2 - 10.1093/gerona/gly174

DO - 10.1093/gerona/gly174

M3 - Journal article

VL - 74

SP - 44

EP - 51

JO - Journals of Gerontology. Series A: Biological Sciences & Medical Sciences

JF - Journals of Gerontology. Series A: Biological Sciences & Medical Sciences

SN - 1079-5006

IS - 1

ER -