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

Mette Soerensen; Serena Dato; Qihua Tan; Mikael Thinggaard; Rabea Kleindorp; Marian Beekman; Rune Jacobsen; H Eka D Suchiman; Anton J M de Craen; Rudi G J Westendorp; Stefan Schreiber; Tinna Stevnsner; Vilhelm A Bohr; P Eline Slagboom; Almut Nebel; James W. Vaupel; Kaare Christensen; Matt McGue; Lene Christiansen

doi:10.1016/j.exger.2012.02.010

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

Mette Soerensen, Serena Dato, Qihua Tan, Mikael Thinggaard, Rabea Kleindorp, Marian Beekman, Rune Jacobsen, H Eka D Suchiman, Anton J M de Craen, Rudi G J Westendorp, Stefan Schreiber, Tinna Stevnsner, Vilhelm A Bohr, P Eline Slagboom, Almut Nebel, James W. Vaupel, Kaare Christensen, Matt McGue, Lene Christiansen

Institut for Molekylærbiologi og Genetik

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

66 Citationer (Scopus)

Abstract

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

Originalsprog	Engelsk
Tidsskrift	Experimental Gerontology
Vol/bind	47
Nummer	5
Sider (fra-til)	379-387
Antal sider	9
ISSN	0531-5565
DOI	https://doi.org/10.1016/j.exger.2012.02.010
Status	Udgivet - maj 2012

Adgang til dokumentet

10.1016/j.exger.2012.02.010

Citationsformater

Soerensen, M., Dato, S., Tan, Q., Thinggaard, M., Kleindorp, R., Beekman, M., Jacobsen, R., Suchiman, H. E. D., de Craen, A. J. M., Westendorp, R. G. J., Schreiber, S., Stevnsner, T., Bohr, V. A., Slagboom, P. E., Nebel, A., Vaupel, J. W., Christensen, K., McGue, M., & Christiansen, L. (2012). 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. Experimental Gerontology, 47(5), 379-387. https://doi.org/10.1016/j.exger.2012.02.010

@article{51674e9c537b4fa59b1a4658c990c2ec,

title = "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",

abstract = "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",

keywords = "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",

author = "Mette Soerensen and Serena Dato and Qihua Tan and Mikael Thinggaard and Rabea Kleindorp and Marian Beekman and Rune Jacobsen and Suchiman, {H Eka D} and {de Craen}, {Anton J M} and Westendorp, {Rudi G J} and Stefan Schreiber and Tinna Stevnsner and Bohr, {Vilhelm A} and Slagboom, {P Eline} and Almut Nebel and Vaupel, {James W.} and Kaare Christensen and Matt McGue and Lene Christiansen",

year = "2012",

month = may,

doi = "10.1016/j.exger.2012.02.010",

language = "English",

volume = "47",

pages = "379--387",

journal = "Experimental Gerontology",

issn = "0531-5565",

publisher = "Elsevier Inc.",

number = "5",

}

Soerensen, M, Dato, S, Tan, Q, Thinggaard, M, Kleindorp, R, Beekman, M, Jacobsen, R, Suchiman, HED, de Craen, AJM, Westendorp, RGJ, Schreiber, S, Stevnsner, T, Bohr, VA, Slagboom, PE, Nebel, A, Vaupel, JW, Christensen, K, McGue, M & Christiansen, L 2012, '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', Experimental Gerontology, bind 47, nr. 5, s. 379-387. https://doi.org/10.1016/j.exger.2012.02.010

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. / Soerensen, Mette; Dato, Serena; Tan, Qihua et al.
I: Experimental Gerontology, Bind 47, Nr. 5, 05.2012, s. 379-387.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes

T2 - cross sectional and longitudinal studies

AU - Soerensen, Mette

AU - Dato, Serena

AU - Tan, Qihua

AU - Thinggaard, Mikael

AU - Kleindorp, Rabea

AU - Beekman, Marian

AU - Jacobsen, Rune

AU - Suchiman, H Eka D

AU - de Craen, Anton J M

AU - Westendorp, Rudi G J

AU - Schreiber, Stefan

AU - Stevnsner, Tinna

AU - Bohr, Vilhelm A

AU - Slagboom, P Eline

AU - Nebel, Almut

AU - Vaupel, James W.

AU - Christensen, Kaare

AU - McGue, Matt

AU - Christiansen, Lene

PY - 2012/5

Y1 - 2012/5

N2 - 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

AB - 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

KW - Aged

KW - Aged, 80 and over

KW - Antioxidants

KW - Case-Control Studies

KW - DNA Damage

KW - DNA Repair

KW - Female

KW - Human Growth Hormone

KW - Humans

KW - Insulin

KW - Insulin-Like Growth Factor I

KW - Longevity

KW - Longitudinal Studies

KW - Male

KW - Middle Aged

KW - Oxidation-Reduction

KW - Polymorphism, Single Nucleotide

KW - Signal Transduction

U2 - 10.1016/j.exger.2012.02.010

DO - 10.1016/j.exger.2012.02.010

M3 - Journal article

C2 - 22406557

SN - 0531-5565

VL - 47

SP - 379

EP - 387

JO - Experimental Gerontology

JF - Experimental Gerontology

IS - 5

ER -

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

Abstract

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