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

doi:10.1093/gerona/gly174

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

Department of Human Biology

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	44-51
Number of pages	8
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	74
Issue number	1
DOIs	https://doi.org/10.1093/gerona/gly174
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/gerona/gly174

Cite this

Sebastiani, P., Gurinovich, A., Nygaard, M., Sasaki, T., Sweigart, B., Bae, H., Andersen, S. L., Villa, F., Atzmon, G., Christensen, K., Arai, Y., Barzilai, N., Puca, A., Christiansen, L., Hirose, N., & Perls, T. T. (2019). APOE Alleles and extreme human longevity. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 74(1), 44-51. https://doi.org/10.1093/gerona/gly174

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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.}",

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: {\textcopyright} 2018 The Author(s). Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.",

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doi = "10.1093/gerona/gly174",

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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', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 74, no. 1, pp. 44-51. https://doi.org/10.1093/gerona/gly174

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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.

N1 - 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.

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

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VL - 74

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JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

IS - 1

ER -

APOE Alleles and extreme human longevity

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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