Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: cross sectional and longitudinal studies

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  • Mette Soerensen, University of Southern Denmark, Denmark
  • Serena Dato, University of Southern Denmark, Denmark
  • Qihua Tan, University of Southern Denmark, Denmark
  • Mikael Thinggaard, University of Southern Denmark, Denmark
  • Rabea Kleindorp, Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Germany
  • Marian Beekman, Department of Molecular Epidemiology, Leiden University Medical Center, Netherlands
  • Rune Jacobsen, Department of Molecular Epidemiology, Leiden University Medical Center, Denmark
  • H Eka D Suchiman, Department of Molecular Epidemiology, Leiden University Medical Center, Netherlands
  • Anton J M de Craen, Department of Gerontology and Geriatrics, Leiden University Medical Center, Netherlands
  • Rudi G J Westendorp, Department of Gerontology and Geriatrics, Leiden University Medical Center, Netherlands
  • Stefan Schreiber, Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Germany
  • Tinna Stevnsner
  • Vilhelm A Bohr, Denmark
  • P Eline Slagboom, Department of Molecular Epidemiology, Leiden University Medical Center, Netherlands
  • Almut Nebel, Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Denmark
  • James W. Vaupel, University of Southern Denmark, Denmark
  • Kaare Christensen, University of Southern Denmark, Denmark
  • Matt McGue, University of Southern Denmark, Denmark
  • Lene Christiansen, University of Southern Denmark, Denmark
Here we explore association with human longevity of common genetic variation in three major candidate pathways: GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidants by investigating 1273 tagging SNPs in 148 genes composing these pathways. In a case-control study of 1089 oldest-old (age 92-93) and 736 middle-aged Danes we found 1 pro/antioxidant SNP (rs1002149 (GSR)), 5 GH/IGF-1/INS SNPs (rs1207362 (KL), rs2267723 (GHRHR), rs3842755 (INS), rs572169 (GHSR), rs9456497 (IGF2R)) and 5 DNA repair SNPs (rs11571461 (RAD52), rs13251813 (WRN), rs1805329 (RAD23B), rs2953983 (POLB), rs3211994 (NTLH1)) to be associated with longevity after correction for multiple testing. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes we found 2 pro/antioxidant SNPs (rs10047589 (TNXRD1), rs207444 (XDH)), 1 GH/IGF-1/INS SNP (rs26802 (GHRL)) and 3 DNA repair SNPs (rs13320360 (MLH1), rs2509049 (H2AFX) and rs705649 (XRCC5)) to be associated with mortality in late life after correction for multiple testing. When examining the 11 SNPs from the case-control study in the longitudinal data, rs3842755 (INS), rs13251813 (WRN) and rs3211994 (NTHL1) demonstrated the same directions of effect (p
Original languageEnglish
JournalExperimental Gerontology
Volume47
Issue5
Pages (from-to)379-387
Number of pages9
ISSN0531-5565
DOIs
Publication statusPublished - May 2012

    Research areas

  • Aged, Aged, 80 and over, Antioxidants, Case-Control Studies, DNA Damage, DNA Repair, Female, Human Growth Hormone, Humans, Insulin, Insulin-Like Growth Factor I, Longevity, Longitudinal Studies, Male, Middle Aged, Oxidation-Reduction, Polymorphism, Single Nucleotide, Signal Transduction

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