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Association of FOXO3A variation with human longevity confirmed in German centenarians
Open accessAbstract
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 (62–64).”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [62]
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Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth457 · Cited by 14,563
A C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387
The plasticity of aging: insights from long-lived mutants
Kenyon, C. (2005) · Cell · doi:10.1016/j.cell.2005.02.002 · Cited by 1,338
Genetic pathways that regulate ageing in model organisms
Guarente, L., & Kenyon, C. J. (2000) · Nature · doi:10.1038/35041700 · Cited by 1,337
Power and Sample Size Calculations for Studies Involving Linear Regression
Dupont, W. D., & Plummer, W. D. (1998) · Controlled Clinical Trials · doi:10.1016/s0197-2456(98)00037-3 · Cited by 1,024
FOXO3A genotype is strongly associated with human longevity
Willcox, B. J., Donlon, T. A., He, Q., Chen, R., Grove, J. S., Yano, K., Masaki, K. H., Willcox, D. C., Rodriguez, B., & Curb, J. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801030105 · Cited by 983
Herskind, A. M., McGue, M., Holm, N. V., Sørensen, T. I. A., Harvald, B., & Vaupel, J. W. (1996) · Human Genetics · doi:10.1007/bf02185763 · Cited by 879
Insulin signaling in health and disease
White, M. F. (2003) · Science · doi:10.1126/science.1092952 · Cited by 733
Mechanisms of aging: public or private?
Partridge, L., & Gems, D. (2002) · Nature Reviews Genetics · doi:10.1038/nrg753 · Cited by 517
Genetic influence on human lifespan and longevity
Hjelmborg, J., Iachine, I. A., Skytthe, A., Vaupel, J. W., McGue, M. K., Koskenvuo, M. J., Kaprio, J. A., Pedersen, N. L., & Christensen, K. (2006) · Human Genetics · doi:10.1007/s00439-006-0144-y · Cited by 498
The quest for genetic determinants of human longevity: challenges and insights
Christensen, K., Johnson, T. E., & Vaupel, J. W. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1871 · Cited by 494
Longevity Is Moderately Heritable in a Sample of Danish Twins Born 1870-1880
McGue, M., Vaupel, J. W., Holm, N. V., & Harvald, B. (1993) · Journal of Gerontology · doi:10.1093/geronj/48.6.b237 · Cited by 364
Do men and women follow different trajectories to reach extreme longevity?
Franceschi, C., Motta, L., Valensin, S., Rapisarda, R., Franzone, A., Berardelli, M., Motta, M., Monti, D., Bonafè, M., Ferrucci, L., et al. (2000) · Aging Clinical and Experimental Research · doi:10.1007/bf03339894 · Cited by 256
Geesaman, B. J., Benson, E. K., Brewster, S. J., Kunkel, L. M., Blanché, H., Thomas, G. D., Perls, T. T., Daly, M. J., & Puca, A. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1936249100 · Cited by 149
Self-citationSNP-Based Analysis of Genetic Substructure in the German Population
Steffens, M., Lamina, C., Illig, T., Bettecken, T., Vogler, R., Entz, P., Suk, E.-K., Toliat, M. R., Klopp, N., Caliebe, A., et al. (2006) · Human Heredity · doi:10.1159/000095850 · Cited by 144
Self-citationLongevity Studies in GenomEUtwin
Skytthe, A., Pedersen, N. L., Kaprio, J. A., Stazi, M. A., Hjelmborg, J., Iachine, I. A., Vaupel, J. W., & Christensen, K. (2003) · Twin Research · doi:10.1375/136905203770326457 · Cited by 137
The Genetics of Exceptional Human Longevity
Perls, T. T., Kunkel, L. M., & Puca, A. A. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.49283.x · Cited by 122
A study of French centenarians: are ACE and APOE associated with longevity?
Blanché, H., Cabanne, L., Sahbatou, M., & Thomas, G. D. (2001) · Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie · doi:10.1016/s0764-4469(00)01274-9 · Cited by 121
Self-citationHaplotypes in the human Foxo1a and Foxo3a genes; impact on disease and mortality at old age
Kuningas, M., Mägi, R., Westendorp, R. G. J., Slagboom, P. E., Remm, M., & van Heemst, D. (2007) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201766 · Cited by 104
An integrated system for high throughput TaqMan™ based SNP genotyping
Hampe, J., Wollstein, A., Lu, T., Frevel, H. J., Will, M., Manaster, C., & Schreiber, S. (2001) · Bioinformatics · doi:10.1093/bioinformatics/17.7.654 · Cited by 102
Self-citationNebel, A., Croucher, P. J. P., Stiegeler, R., Nikolaus, S., Krawczak, M., & Schreiber, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408670102 · Cited by 96
Self-citationPower for Genetic Association Study of Human Longevity Using the Case-Control Design
Tan, Q., Zhao, J., Zhang, D., Kruse, T. A., & Christensen, K. (2008) · American Journal of Epidemiology · doi:10.1093/aje/kwn205 · Cited by 39
Gems, D., & McElwee, J. J. (2003) · Nature · doi:10.1038/424259a · Cited by 29
GENOMIZER: an integrated analysis system for genome-wide association data
Franke, A., Wollstein, A., Teuber, M., Wittig, M., Lu, T. T., Hoffmann, K., Nürnberg, P., Krawczak, M., Schreiber, S., & Hampe, J. (2006) · Human Mutation · doi:10.1002/humu.20306 · Cited by 28
Self-citationAllelic Variation and Human Longevity
Nebel, A., & Schreiber, S. (2005) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2005.29.pe23 · Cited by 11
Self-citation
Research works printed but not linked: 1
- A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, 2008).
Cited by
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Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739
Facing up to the global challenges of ageing
Partridge, L., Deelen, J., & Slagboom, P. E. (2018) · Nature · doi:10.1038/s41586-018-0457-8 · Cited by 1,475
HIV Infection, Inflammation, Immunosenescence, and Aging
Deeks, S. G. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-042909-093756 · Cited by 1,349
Neural mechanisms of ageing and cognitive decline
Bishop, N. A., Lu, T., & Yankner, B. A. (2010) · Nature · doi:10.1038/nature08983 · Cited by 1,323
Mertens, J., Paquola, A. C. M., Ku, M., Hatch, E., Böhnke, L., Ladjevardi, S., McGrath, S., Campbell, B., Lee, H., Herdy, J. R., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.09.001 · Cited by 765
Metadata
- 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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