OR18-2 Higher Plasma Estradiol Concentration Is Independently Associated with Lower Biological Age, Assessed as Leucocyte Telomere Length, in Older Men

Bu Yeap, Jennie Hui, Matthew Knuiman, David Handelsman, Leon Flicker, Mark Divitini, Gillian Arscott, Susan McLennan, Stephen Twigg, Osvaldo Almeida, Graeme Hankey, Jonathan Golledge, Paul Norman, John Beilby

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Abstract

Telomeres are essential DNA-protein complexes comprising TTAGGG repeats binding specific proteins, which protect the physical ends of chromosomes from fusion and degradation. Attrition of telomeres results in cellular senescence. Leucocyte telomere length (LTL) reflects lengths of telomeres in various tissues, and shorter LTL is a marker of advancing biological age. Previous work has associated bioactive metabolites of T, dihydrotestosterone (DHT) and estradiol (E2) with LTL in a population of predominantly middle-aged men [1]. However, the relationship of these hormones to biological age in older men was unclear. We aimed to clarify associations of sex hormones with LTL in a cohort of 2,913 community-dwelling men aged 70-89 years. Early morning blood samples were assayed for T, DHT and E2 using mass spectrometry, and for sex hormone-binding globulin (SHBG) using immunoassay. LTL was measured using a multiplex quantitative PCR method and expressed as the amount of telomeric DNA relative to beta-globin, a single copy control gene (T/S ratio). Cross-sectional analyses utilised multivariable linear regression. Mean (±SD) age was 76.7±3.2 years. The average difference per decade of age was T -0.46 nmol/L, DHT -0.11 nmol/L, E2 -7.5 pmol/L, SHBG +10.2 nmol/L, and LTL (T/S ratio) -0.065. E2 correlated with T/S ratio (r=0.038, p=0.039). After excluding highest and lowest 1% of values, the correlation between E2 and T/S ratio was largely unchanged (r=0.039, p=0.037). SHBG was inversely correlated with T/S ratio (r=-0.053, p=0.004), also unchanged in the trimmed analysis (r=-0.055, p=0.004.) After adjusting for age, BMI, cardiovascular disease, diabetes, alcohol, smoking, physical activity, lipids and hypertension, E2 remained associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, p=0.043). When E2 and SHBG were simultaneously included in the multivariate model, E2 remained positively associated with T/S ratio (coefficient 0.014, p=0.014) and SHBG inversely associated (coefficient -0.013, p=0.037). The magnitude of increase in T/S ratio associated with a 1 SD higher plasma E2 concentration was comparable with having a BMI 3.6 kg/m2 lower, and two thirds that associated with being 3.6 years younger. T, DHT and LH were not associated with LTL in multivariate analyses. To conclude, in older men, neither T nor DHT are associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated. These findings associate activity of the gonadal axis with lower biological age in older men. However, causality cannot be inferred from an observational, cross-sectional study, thus additional research is necessary to determine whether sex hormone exposure modulates male biological ageing. Reference: [1] Yeap BB, et al. J Clin Endocrinol Metab 2016; 101: 1299-1306.
Original languageEnglish
JournalJournal of the Endocrine Society
Volume3
Issue numberSupplement_1
DOIs
Publication statusPublished - 30 Apr 2019

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Telomere
Estradiol
Leukocytes
Sex Hormone-Binding Globulin
Dihydrotestosterone
Gonadal Steroid Hormones
Cross-Sectional Studies
Independent Living
beta-Globins
Cell Aging
Multiplex Polymerase Chain Reaction
DNA
Immunoassay
Causality
Linear Models
Mass Spectrometry
Carrier Proteins
Cardiovascular Diseases
Multivariate Analysis
Chromosomes

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@article{aaa3157e19fa4fd2976cfee6f5daf5ff,
title = "OR18-2 Higher Plasma Estradiol Concentration Is Independently Associated with Lower Biological Age, Assessed as Leucocyte Telomere Length, in Older Men",
abstract = "Telomeres are essential DNA-protein complexes comprising TTAGGG repeats binding specific proteins, which protect the physical ends of chromosomes from fusion and degradation. Attrition of telomeres results in cellular senescence. Leucocyte telomere length (LTL) reflects lengths of telomeres in various tissues, and shorter LTL is a marker of advancing biological age. Previous work has associated bioactive metabolites of T, dihydrotestosterone (DHT) and estradiol (E2) with LTL in a population of predominantly middle-aged men [1]. However, the relationship of these hormones to biological age in older men was unclear. We aimed to clarify associations of sex hormones with LTL in a cohort of 2,913 community-dwelling men aged 70-89 years. Early morning blood samples were assayed for T, DHT and E2 using mass spectrometry, and for sex hormone-binding globulin (SHBG) using immunoassay. LTL was measured using a multiplex quantitative PCR method and expressed as the amount of telomeric DNA relative to beta-globin, a single copy control gene (T/S ratio). Cross-sectional analyses utilised multivariable linear regression. Mean (±SD) age was 76.7±3.2 years. The average difference per decade of age was T -0.46 nmol/L, DHT -0.11 nmol/L, E2 -7.5 pmol/L, SHBG +10.2 nmol/L, and LTL (T/S ratio) -0.065. E2 correlated with T/S ratio (r=0.038, p=0.039). After excluding highest and lowest 1{\%} of values, the correlation between E2 and T/S ratio was largely unchanged (r=0.039, p=0.037). SHBG was inversely correlated with T/S ratio (r=-0.053, p=0.004), also unchanged in the trimmed analysis (r=-0.055, p=0.004.) After adjusting for age, BMI, cardiovascular disease, diabetes, alcohol, smoking, physical activity, lipids and hypertension, E2 remained associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, p=0.043). When E2 and SHBG were simultaneously included in the multivariate model, E2 remained positively associated with T/S ratio (coefficient 0.014, p=0.014) and SHBG inversely associated (coefficient -0.013, p=0.037). The magnitude of increase in T/S ratio associated with a 1 SD higher plasma E2 concentration was comparable with having a BMI 3.6 kg/m2 lower, and two thirds that associated with being 3.6 years younger. T, DHT and LH were not associated with LTL in multivariate analyses. To conclude, in older men, neither T nor DHT are associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated. These findings associate activity of the gonadal axis with lower biological age in older men. However, causality cannot be inferred from an observational, cross-sectional study, thus additional research is necessary to determine whether sex hormone exposure modulates male biological ageing. Reference: [1] Yeap BB, et al. J Clin Endocrinol Metab 2016; 101: 1299-1306.",
author = "Bu Yeap and Jennie Hui and Matthew Knuiman and David Handelsman and Leon Flicker and Mark Divitini and Gillian Arscott and Susan McLennan and Stephen Twigg and Osvaldo Almeida and Graeme Hankey and Jonathan Golledge and Paul Norman and John Beilby",
year = "2019",
month = "4",
day = "30",
doi = "10.1210/js.2019-or18-2",
language = "English",
volume = "3",
journal = "Journal of the Endocrine Society",
issn = "2472-1972",
publisher = "ENDOCRINE SOC",
number = "Supplement_1",

}

TY - JOUR

T1 - OR18-2 Higher Plasma Estradiol Concentration Is Independently Associated with Lower Biological Age, Assessed as Leucocyte Telomere Length, in Older Men

AU - Yeap, Bu

AU - Hui, Jennie

AU - Knuiman, Matthew

AU - Handelsman, David

AU - Flicker, Leon

AU - Divitini, Mark

AU - Arscott, Gillian

AU - McLennan, Susan

AU - Twigg, Stephen

AU - Almeida, Osvaldo

AU - Hankey, Graeme

AU - Golledge, Jonathan

AU - Norman, Paul

AU - Beilby, John

PY - 2019/4/30

Y1 - 2019/4/30

N2 - Telomeres are essential DNA-protein complexes comprising TTAGGG repeats binding specific proteins, which protect the physical ends of chromosomes from fusion and degradation. Attrition of telomeres results in cellular senescence. Leucocyte telomere length (LTL) reflects lengths of telomeres in various tissues, and shorter LTL is a marker of advancing biological age. Previous work has associated bioactive metabolites of T, dihydrotestosterone (DHT) and estradiol (E2) with LTL in a population of predominantly middle-aged men [1]. However, the relationship of these hormones to biological age in older men was unclear. We aimed to clarify associations of sex hormones with LTL in a cohort of 2,913 community-dwelling men aged 70-89 years. Early morning blood samples were assayed for T, DHT and E2 using mass spectrometry, and for sex hormone-binding globulin (SHBG) using immunoassay. LTL was measured using a multiplex quantitative PCR method and expressed as the amount of telomeric DNA relative to beta-globin, a single copy control gene (T/S ratio). Cross-sectional analyses utilised multivariable linear regression. Mean (±SD) age was 76.7±3.2 years. The average difference per decade of age was T -0.46 nmol/L, DHT -0.11 nmol/L, E2 -7.5 pmol/L, SHBG +10.2 nmol/L, and LTL (T/S ratio) -0.065. E2 correlated with T/S ratio (r=0.038, p=0.039). After excluding highest and lowest 1% of values, the correlation between E2 and T/S ratio was largely unchanged (r=0.039, p=0.037). SHBG was inversely correlated with T/S ratio (r=-0.053, p=0.004), also unchanged in the trimmed analysis (r=-0.055, p=0.004.) After adjusting for age, BMI, cardiovascular disease, diabetes, alcohol, smoking, physical activity, lipids and hypertension, E2 remained associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, p=0.043). When E2 and SHBG were simultaneously included in the multivariate model, E2 remained positively associated with T/S ratio (coefficient 0.014, p=0.014) and SHBG inversely associated (coefficient -0.013, p=0.037). The magnitude of increase in T/S ratio associated with a 1 SD higher plasma E2 concentration was comparable with having a BMI 3.6 kg/m2 lower, and two thirds that associated with being 3.6 years younger. T, DHT and LH were not associated with LTL in multivariate analyses. To conclude, in older men, neither T nor DHT are associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated. These findings associate activity of the gonadal axis with lower biological age in older men. However, causality cannot be inferred from an observational, cross-sectional study, thus additional research is necessary to determine whether sex hormone exposure modulates male biological ageing. Reference: [1] Yeap BB, et al. J Clin Endocrinol Metab 2016; 101: 1299-1306.

AB - Telomeres are essential DNA-protein complexes comprising TTAGGG repeats binding specific proteins, which protect the physical ends of chromosomes from fusion and degradation. Attrition of telomeres results in cellular senescence. Leucocyte telomere length (LTL) reflects lengths of telomeres in various tissues, and shorter LTL is a marker of advancing biological age. Previous work has associated bioactive metabolites of T, dihydrotestosterone (DHT) and estradiol (E2) with LTL in a population of predominantly middle-aged men [1]. However, the relationship of these hormones to biological age in older men was unclear. We aimed to clarify associations of sex hormones with LTL in a cohort of 2,913 community-dwelling men aged 70-89 years. Early morning blood samples were assayed for T, DHT and E2 using mass spectrometry, and for sex hormone-binding globulin (SHBG) using immunoassay. LTL was measured using a multiplex quantitative PCR method and expressed as the amount of telomeric DNA relative to beta-globin, a single copy control gene (T/S ratio). Cross-sectional analyses utilised multivariable linear regression. Mean (±SD) age was 76.7±3.2 years. The average difference per decade of age was T -0.46 nmol/L, DHT -0.11 nmol/L, E2 -7.5 pmol/L, SHBG +10.2 nmol/L, and LTL (T/S ratio) -0.065. E2 correlated with T/S ratio (r=0.038, p=0.039). After excluding highest and lowest 1% of values, the correlation between E2 and T/S ratio was largely unchanged (r=0.039, p=0.037). SHBG was inversely correlated with T/S ratio (r=-0.053, p=0.004), also unchanged in the trimmed analysis (r=-0.055, p=0.004.) After adjusting for age, BMI, cardiovascular disease, diabetes, alcohol, smoking, physical activity, lipids and hypertension, E2 remained associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, p=0.043). When E2 and SHBG were simultaneously included in the multivariate model, E2 remained positively associated with T/S ratio (coefficient 0.014, p=0.014) and SHBG inversely associated (coefficient -0.013, p=0.037). The magnitude of increase in T/S ratio associated with a 1 SD higher plasma E2 concentration was comparable with having a BMI 3.6 kg/m2 lower, and two thirds that associated with being 3.6 years younger. T, DHT and LH were not associated with LTL in multivariate analyses. To conclude, in older men, neither T nor DHT are associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated. These findings associate activity of the gonadal axis with lower biological age in older men. However, causality cannot be inferred from an observational, cross-sectional study, thus additional research is necessary to determine whether sex hormone exposure modulates male biological ageing. Reference: [1] Yeap BB, et al. J Clin Endocrinol Metab 2016; 101: 1299-1306.

U2 - 10.1210/js.2019-or18-2

DO - 10.1210/js.2019-or18-2

M3 - Article

VL - 3

JO - Journal of the Endocrine Society

JF - Journal of the Endocrine Society

SN - 2472-1972

IS - Supplement_1

ER -