Associations of plasma IGF1, IGFBP3 and estradiol with leucocyte telomere length, a marker of biological age, in men

Bu Beng Yeap, Jennie Hui, Matthew Knuiman, S A Chubb, Ken K Y Ho, Leon Flicker, Mark L Divitini, Gillian M Arscott, Stephen Twigg, Osvaldo Almeida, Graeme Hankey, Jonathan Golledge, John Beilby

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Abstract

OBJECTIVE: Effects of insulin-like growth factor 1 (IGF1) and its binding proteins (IGFBPs) on ageing, and their interaction with sex hormones, remain uncertain. We examined associations of plasma IGF1, IGFBP1, IGFBP3, estradiol and testosterone, with leucocyte telomere length (LTL), a marker of biological age, in 2999 community-dwelling men aged 70-84 years.

METHODS: Plasma IGF1, IGFBP1 and IGFBP3 measured using immunoassay, sex hormones using mass spectrometry. LTL measured by PCR, expressed as ratio of telomeric to single-copy control gene DNA (T/S ratio). Linear regression models adjusted for age and cardiometabolic risk factors, median splits defined low/high groups.

RESULTS: Mean age was 76.7±3.2 years. IGF1 and IGFBP3 showed age-adjusted correlations with LTL (coefficient 0.59, p=0.001 and 0.45, p=0.013 respectively), IGFBP1 did not. In multivariable-adjusted models IGF1 and IGFBP3 (but not IGFBP1) were associated with LTL (T/S ratio 0.015 higher per 1SD increase in IGF1, p=0.007, and 0.011 per 1SD IGFBP3, p=0.049). IGF1 and estradiol were independently associated with longer telomeres (T/S ratio 0.012 higher per 1SD increase in estradiol, p=0.027, when included in model with IGF1). Testosterone was not associated with LTL. Men with both high IGF1 (>133 ug/L) and high estradiol (>70 pmol/L) had longer LTL compared to men with lower values (multivariable-adjusted T/S ratio 1.20 vs 1.16, p=0.018).

CONCLUSIONS: Higher IGF1 and IGFBP3 are independently associated with longer telomeres in older men. Additive associations of higher IGF1 and higher estradiol with telomere length are present. Further studies are needed to determine whether these hormonal exposures cooperate to slow biological ageing.

Original languageEnglish
JournalEuropean Journal of Endocrinology
DOIs
Publication statusE-pub ahead of print - 1 Oct 2019

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Telomere
Somatomedins
Estradiol
Leukocytes
Biomarkers
Gonadal Steroid Hormones
Testosterone
Linear Models
Independent Living
Insulin-Like Growth Factor Binding Protein 1
Immunoassay
Mass Spectrometry
Polymerase Chain Reaction

Cite this

@article{4e337e3799ee40e4966f3f32e920e666,
title = "Associations of plasma IGF1, IGFBP3 and estradiol with leucocyte telomere length, a marker of biological age, in men",
abstract = "OBJECTIVE: Effects of insulin-like growth factor 1 (IGF1) and its binding proteins (IGFBPs) on ageing, and their interaction with sex hormones, remain uncertain. We examined associations of plasma IGF1, IGFBP1, IGFBP3, estradiol and testosterone, with leucocyte telomere length (LTL), a marker of biological age, in 2999 community-dwelling men aged 70-84 years.METHODS: Plasma IGF1, IGFBP1 and IGFBP3 measured using immunoassay, sex hormones using mass spectrometry. LTL measured by PCR, expressed as ratio of telomeric to single-copy control gene DNA (T/S ratio). Linear regression models adjusted for age and cardiometabolic risk factors, median splits defined low/high groups.RESULTS: Mean age was 76.7±3.2 years. IGF1 and IGFBP3 showed age-adjusted correlations with LTL (coefficient 0.59, p=0.001 and 0.45, p=0.013 respectively), IGFBP1 did not. In multivariable-adjusted models IGF1 and IGFBP3 (but not IGFBP1) were associated with LTL (T/S ratio 0.015 higher per 1SD increase in IGF1, p=0.007, and 0.011 per 1SD IGFBP3, p=0.049). IGF1 and estradiol were independently associated with longer telomeres (T/S ratio 0.012 higher per 1SD increase in estradiol, p=0.027, when included in model with IGF1). Testosterone was not associated with LTL. Men with both high IGF1 (>133 ug/L) and high estradiol (>70 pmol/L) had longer LTL compared to men with lower values (multivariable-adjusted T/S ratio 1.20 vs 1.16, p=0.018).CONCLUSIONS: Higher IGF1 and IGFBP3 are independently associated with longer telomeres in older men. Additive associations of higher IGF1 and higher estradiol with telomere length are present. Further studies are needed to determine whether these hormonal exposures cooperate to slow biological ageing.",
author = "Yeap, {Bu Beng} and Jennie Hui and Matthew Knuiman and Chubb, {S A} and Ho, {Ken K Y} and Leon Flicker and Divitini, {Mark L} and Arscott, {Gillian M} and Stephen Twigg and Osvaldo Almeida and Graeme Hankey and Jonathan Golledge and John Beilby",
year = "2019",
month = "10",
day = "1",
doi = "10.1530/EJE-19-0638",
language = "English",
journal = "European Journal of Endocrinology,",
issn = "0804-4643",
publisher = "BioScientifica Ltd",

}

TY - JOUR

T1 - Associations of plasma IGF1, IGFBP3 and estradiol with leucocyte telomere length, a marker of biological age, in men

AU - Yeap, Bu Beng

AU - Hui, Jennie

AU - Knuiman, Matthew

AU - Chubb, S A

AU - Ho, Ken K Y

AU - Flicker, Leon

AU - Divitini, Mark L

AU - Arscott, Gillian M

AU - Twigg, Stephen

AU - Almeida, Osvaldo

AU - Hankey, Graeme

AU - Golledge, Jonathan

AU - Beilby, John

PY - 2019/10/1

Y1 - 2019/10/1

N2 - OBJECTIVE: Effects of insulin-like growth factor 1 (IGF1) and its binding proteins (IGFBPs) on ageing, and their interaction with sex hormones, remain uncertain. We examined associations of plasma IGF1, IGFBP1, IGFBP3, estradiol and testosterone, with leucocyte telomere length (LTL), a marker of biological age, in 2999 community-dwelling men aged 70-84 years.METHODS: Plasma IGF1, IGFBP1 and IGFBP3 measured using immunoassay, sex hormones using mass spectrometry. LTL measured by PCR, expressed as ratio of telomeric to single-copy control gene DNA (T/S ratio). Linear regression models adjusted for age and cardiometabolic risk factors, median splits defined low/high groups.RESULTS: Mean age was 76.7±3.2 years. IGF1 and IGFBP3 showed age-adjusted correlations with LTL (coefficient 0.59, p=0.001 and 0.45, p=0.013 respectively), IGFBP1 did not. In multivariable-adjusted models IGF1 and IGFBP3 (but not IGFBP1) were associated with LTL (T/S ratio 0.015 higher per 1SD increase in IGF1, p=0.007, and 0.011 per 1SD IGFBP3, p=0.049). IGF1 and estradiol were independently associated with longer telomeres (T/S ratio 0.012 higher per 1SD increase in estradiol, p=0.027, when included in model with IGF1). Testosterone was not associated with LTL. Men with both high IGF1 (>133 ug/L) and high estradiol (>70 pmol/L) had longer LTL compared to men with lower values (multivariable-adjusted T/S ratio 1.20 vs 1.16, p=0.018).CONCLUSIONS: Higher IGF1 and IGFBP3 are independently associated with longer telomeres in older men. Additive associations of higher IGF1 and higher estradiol with telomere length are present. Further studies are needed to determine whether these hormonal exposures cooperate to slow biological ageing.

AB - OBJECTIVE: Effects of insulin-like growth factor 1 (IGF1) and its binding proteins (IGFBPs) on ageing, and their interaction with sex hormones, remain uncertain. We examined associations of plasma IGF1, IGFBP1, IGFBP3, estradiol and testosterone, with leucocyte telomere length (LTL), a marker of biological age, in 2999 community-dwelling men aged 70-84 years.METHODS: Plasma IGF1, IGFBP1 and IGFBP3 measured using immunoassay, sex hormones using mass spectrometry. LTL measured by PCR, expressed as ratio of telomeric to single-copy control gene DNA (T/S ratio). Linear regression models adjusted for age and cardiometabolic risk factors, median splits defined low/high groups.RESULTS: Mean age was 76.7±3.2 years. IGF1 and IGFBP3 showed age-adjusted correlations with LTL (coefficient 0.59, p=0.001 and 0.45, p=0.013 respectively), IGFBP1 did not. In multivariable-adjusted models IGF1 and IGFBP3 (but not IGFBP1) were associated with LTL (T/S ratio 0.015 higher per 1SD increase in IGF1, p=0.007, and 0.011 per 1SD IGFBP3, p=0.049). IGF1 and estradiol were independently associated with longer telomeres (T/S ratio 0.012 higher per 1SD increase in estradiol, p=0.027, when included in model with IGF1). Testosterone was not associated with LTL. Men with both high IGF1 (>133 ug/L) and high estradiol (>70 pmol/L) had longer LTL compared to men with lower values (multivariable-adjusted T/S ratio 1.20 vs 1.16, p=0.018).CONCLUSIONS: Higher IGF1 and IGFBP3 are independently associated with longer telomeres in older men. Additive associations of higher IGF1 and higher estradiol with telomere length are present. Further studies are needed to determine whether these hormonal exposures cooperate to slow biological ageing.

U2 - 10.1530/EJE-19-0638

DO - 10.1530/EJE-19-0638

M3 - Article

JO - European Journal of Endocrinology,

JF - European Journal of Endocrinology,

SN - 0804-4643

ER -