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 V. Stevnsner; Vilhelm 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 V. Stevnsner, Vilhelm Bohr, P Eline Slagboom, Almut Nebel, James W Vaupel, Kaare Christensen, Matt McGue, Lene Christiansen

Research output: Contribution to journal › Journal article › Research › peer-review

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 11years 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 language	English
Journal	Experimental Gerontology
Volume	47
Issue number	5
Pages (from-to)	379-87
Number of pages	9
ISSN	0531-5565
DOIs	https://doi.org/10.1016/j.exger.2012.02.010
Publication status	Published - May 2012

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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. V., Bohr, V., 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), 379-87. https://doi.org/10.1016/j.exger.2012.02.010

@article{8e146096d49a4ade93032ab71b5399f8,

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 11years 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",

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 Stevnsner, {Tinna V.} and Vilhelm Bohr 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--87",

journal = "Experimental Gerontology",

issn = "0531-5565",

publisher = "Elsevier",

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Soerensen, M, Dato, S, Tan, Q , Thinggaard, M, Kleindorp, R, Beekman, M, Jacobsen, R, Suchiman, HED, de Craen, AJM, Westendorp, RGJ, Schreiber, S, Stevnsner, TV, Bohr, V, 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, vol. 47, no. 5, pp. 379-87. 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.

In: Experimental Gerontology, Vol. 47, No. 5, 05.2012, p. 379-87.

Research output: Contribution to journal › Journal article › Research › 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 V.

AU - Bohr, Vilhelm

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 11years 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 11years 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

U2 - 10.1016/j.exger.2012.02.010

DO - 10.1016/j.exger.2012.02.010

M3 - Journal article

C2 - 22406557

VL - 47

SP - 379

EP - 387

JO - Experimental Gerontology

JF - Experimental Gerontology

SN - 0531-5565

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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