Association of FOXO3A variation with human longevity confirmed in German centenarians
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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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Polymorphisms in two IIS pathway genes, the IGF-1 receptor and the downstream FOXO3 transcription factor, have been associated with longevity and healthy ageing in humans.
“Polymorphisms in two IIS pathway genes, the IGF-1 receptor and the downstream FOXO3 transcription factor, have been associated with longevity and healthy ageing in humans (62–64).”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [62]
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“Recently, the FOXO gene family has been identified as a candidate for human longevity (Lunetta et al., 2007; Willcox et al., 2008; Anselmi et al., 2009; Flachsbart et al., 2009; Li et al., 2009).”
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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
- 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
- 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
- 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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