Cited by 572FOXO transcription factor regulationGenetics, Aging, and Longevity in Model OrganismsGenetic Associations and Epidemiology

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Association of FOXO3A variation with human longevity confirmed in German centenarians

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Flachsbart, Friederike, Caliebe, Amke, Kleindorp, Rabea, Blanché, Hélène, von Eller-Eberstein, Huberta, Nikolaus, Susanna, Schreiber, Stefan, Nebel, Almut·2009·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0809594106PMC PMC2650329

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Abstract

The human forkhead box O3A gene ( FOXO3A ) encodes an evolutionarily conserved key regulator of the insulin–IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry [Willcox et al. (2008) Proc Natl Acad Sci USA 105:13987–13992]. However, this finding required replication in an independent population. Here, we have investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provide evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age. The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research. Our study extended the initial finding observed in Japanese men to women and indicates that both genders were likely to be equally affected by variation in FOXO3A . Replication in a French centenarian sample generated a trend that supported the previous results. Our findings confirmed the initial discovery in the Japanese sample and indicate FOXO3A as a susceptibility gene for prolonged survival in humans.

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Authors: Flachsbart, F., Caliebe, A., Kleindorp, R., Blanché, H., von Eller-Eberstein, H., Nikolaus, S., Schreiber, S., & Nebel, A.
Affiliations: Christian-Albrechts-Universität zu Kiel (DE)
Institute of Medical Informatics and Statistics, and
Institute of Clinical Molecular Biology,
Fondation Jean Dausset-CEPH (FR)
Popgen Biobank, Christian-Albrechts-University, 24105 Kiel, Germany; and
Corresponding author: Schreiber, Stefan
ORCID: Caliebe, Amke
Blanché, Hélène
Nikolaus, Susanna
Schreiber, Stefan
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2009-02-24
Volume: 106
Issue: 8
Pages: 2700-2705
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0809594106
PMC: PMC2650329
OpenAlex: W1965684670
Cited by: 572
References: 27
Citations by year: 2026: 12 · 2025: 8 · 2024: 19 · 2023: 11 · 2022: 14 · 2021: 24 · 2020: 27 · 2019: 30 · 2018: 34 · 2017: 37 · 2016: 31 · 2015: 40 · 2014: 54 · 2013: 51 · 2012: 48
FWCI: 24.13
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.pnas.org/site/misc/userlicense.xhtml (vor, 181 d)
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: European Commission
Deutsche Forschungsgemeinschaft
Exzellenzclusters Entzündungsforschung
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: FOXO3, human longevity, centenarians, single nucleotide polymorphisms, insulin/IGF-1 signaling, replication study, sex differences in longevity
MeSH terms: Forkhead Box Protein O3, Adolescent, Adult, Aged, Aged, 80 and over, Humans, Longevity, Middle Aged, Genetic Variation, Case-Control Studies, Polymorphism, Single Nucleotide, Forkhead Transcription Factors

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Association of FOXO3A variation with human longevity confirmed in German centenarians

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