{
  "titles": [
    "2011 - Genomics of human longevity.pdf",
    "2015 - A Chromosome 13 locus is associated with male-specific mortality in mice.pdf",
    "2012 - Genome-Environment Interactions That Modulate.pdf",
    "2013 - Genome Instability and Aging.pdf",
    "2020 - Clinical Genetics and Genomics of Aging.pdf",
    "2020 - Clinical Genetics and Genomics of Aging.pdf",
    "2011 - A genome-wide association study confirms APOE as the major gene influencing.pdf",
    "2019 - A meta-analysis of genome-wide association.pdf",
    "2020 - Clinical Genetics and Genomics of Aging.pdf",
    "2015 - A Chromosome 13 locus is associated with male-specific mortality in mice.pdf"
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    "27 Willcox, B. J. et al. 2008 FOXO3A genotype is strongly associated with human longevity. Proc. Natl Acad. Sci. USA 105, 13 98713 992. ( doi:10.1073/ pnas.0801030105 ) 28 Flachsbart, F., Caliebe, A., Kleindorp, R., Blanche, H., von Eller-Eberstein, H., Nikolaus, S., Schreiber, S. & Nebela, A. 2009 Association of FOXO3A variationwith human longevity conrmed in GermanGenomics of human longevity P . E. Slagboom et al. 41",
    "3. Willcox BJ, Donlon TA, He Q et al (2008) FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA 105(37):1398713992. doi: 10.1073/pnas.0801030105 4. Anselmi CV, Malovini A, Roncarati R et al (2009) Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res 12(2):95104. doi: 10.1089/ rej.2008.0827 5. Flachsbart F, Caliebe A, Kleindorp R et al (2009) Association of FOXO3A variation with human longevity conrmed in German",
    "are, in fact, part of the same insulin/IGF1/GH pathway(Fig. 1) that modulates lifespan across organisms (Ke-nyon, 2010). A strong association between FOXO3 and human longevity has been reported (Willcox et al., 2008)and subsequently validated in other populations (forreview, see Kenyon, 2010). FOXO3 was also associatedAGING GENES AS TARGETS FOR DRUG DISCOVERY 95",
    "Biogerontology 11:28797 117. Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, et al. 2008. FOXO3A genotype is strongly associated with human longevity. Proc. Natl. Acad. Sci. USA 105:1398792 118. Soerensen M, Dato S, Christensen K, McGue M, Stevnsner T, et al. 2010. Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data. Aging Cell 9:101017 119. Mardis ER. 2011. A decades perspective on DNA sequencing technology. Nature 470:198203",
    "FOXO3 locus is associated with extreme longevity in humans (centenarians) [2,  58, 59]. NRF/SKN-1 activates the expression of genes involved in protecting the cell in  response to ROS, toxins, and metabolic changes through mTOR and insulin/IGF  signaling, and it is also dysregulated later in life [60, 61]. Increasing the levels of  L. Garca-Velzquez and C. Arias",
    "A. 2003;100:406671. https://doi.org/10.1073/pnas.2628028100.  24. van den Akker EB, Deelen J, Slagboom PE, Beekman M. Exome and whole genome  sequencing in aging and longevity. Adv Exp Med Biol. 2015;847:12739. https://doi. org/10.1007/978-1-4939-2404-2_6.  25. Flachsbart F, etal. Association of FOXO3A variation with human longevity confirmed in  German centenarians. Proc Natl Acad Sci U S A. 2009;106:27005. https://doi.org/10.1073/ pnas.0809594106. A. Garca-Venzor and E. A. Mandujano-Tinoco",
    "X.L.,  2009.  Genetic  association  of  FOXO1A  and  FOXO3A  with  longevity  trait  in Han  Chinese  populations.  Hum.  Mol.  Genet.  18,  48974904. Lunetta,  K.L.,  DAgostino  Sr.,  R.B.,  Karasik,  D.,  Benjamin,  E.J.,  Guo,  C.Y.,  Govindaraju, R.,  Kiel,  D.P.,  Kelly-Hayes,  M.,  Massaro,  J.M.,  Pencina,  M.J.,  Seshadri,  S.,  Murabito, J.M.,  2007.  Genetic  correlates  of  longevity  and  selected  age-related  phenotypes:",
    "theFOXO3 locus is not surprising, since this locus was previously reported in the longevity GWA study from the CHARGE con- sortium 7, from which many cohorts are included in these meta- analyses. So far, three functional longevity-associated variants have been identi ed at the FOXO3 locus (rs2802292, rs12206094, and rs4946935). For all of them, an allele-speci c response to cellular stress was observed. Consistently, the longevity-associated alleles of all three variants were shown to induce FOXO3",
    "exceptional longevity with no significant genetic contribution. Interestingly, the  authors found that FOXO3A, a longevity allele, may not be related to healthy aging  phenotype [29]. Aging is a complex process usually accompanied by the onset of different dis- eases like neurodegenerative disorders (Alzheimers disease and Parkinsons dis- ease), cardiovascular illnesses, and cancer. The study of the genetic basis of these  aging-related diseases is another approach in the study of the genomic basis of",
    "centenarians. Proc Natl Acad Sci USA 106(8):27002705. doi: 10. 1073/pnas.0809594106 6. Li Y, Wang WJ, Cao H et al (2009) Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet 18(24):48974904. doi: 10.1093/ hmg/ddp459 7. Soerensen M, Dato S, Christensen K et al (2010) Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data. AgingCell 9(6):10101017. doi: 10.1111/j.1474-9726.2010.00627.x"
  ],
  "answer": "The gene FOXO3 plays a significant role in human longevity. Multiple studies have shown a strong association between variations in the FOXO3 gene and increased lifespan. For instance, the FOXO3A genotype has been strongly linked with human longevity, as demonstrated in studies by Willcox et al. (2008) and confirmed in various populations, including German and Southern Italian centenarians [1], [2], [3]. The FOXO3 locus is associated with extreme longevity in humans, particularly among centenarians [5]. Additionally, specific variants at the FOXO3 locus have been identified that respond to cellular stress, which may contribute to their role in promoting longevity [8].",
  "question": "What is the role of the gene FOXO3 in longevity?"
}