Oral Presentation ESA-SRB-AOTA 2019

Plasma insulin-like growth factor-I, IGF binding protein 3 and estradiol are associated with longer leucocyte telomere length, a marker of lower biological age, in older men. (#56)

Bu B Yeap 1 2 , Jennie Hui 3 , Matthew W Knuiman 4 , Paul Chubb 5 , Ken KY Ho 6 , Mark L Divitini 4 , Gillian M Arscott 3 , Stephen M Twigg 7 , Susan V McLennan 7 , Leon Flicker 1 8 , John P Beilby 3
  1. The Medical School, University of Western Australia, Perth, WA, Australia
  2. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia
  3. PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
  4. School of Population and Global Health, University of Western Australia, Perth, WA, Australia
  5. PathWest Laboratory Medicine, Fiona Stanley Hospital, Perth, WA, Australia
  6. Garvan Institute of Medical Research, Sydney, NSW, Australia
  7. Department of Endocrinology, University of Sydney, Sydney, NSW, Australia
  8. WA Centre for Health and Ageing, University of Western Australia, Perth, WA, Australia

Introduction

Telomeres are essential DNA-protein complexes which protect the physical ends of chromosomes. Leucocyte telomere length (LTL) reflects length of telomeres in tissues, and shorter LTL marks advancing biological age. Estradiol is associated with LTL [1,2], but the influence of insulin-like growth factor-I (IGF-I) remains uncertain. We examined associations of plasma IGF-I, it’s binding proteins 1 and 3 (IGFBP1 and IGFBP3) and estradiol with LTL in 2,999 community-dwelling men aged 70-84 years.

Methods

Plasma IGF-I, IGFBP1 and IGFBP3 measured using immunoassay and sex hormones using mass spectrometry. LTL measured by PCR, expressed as the ratio of telomeric to single-copy control gene DNA (T/S ratio). Linear regression models adjusted for age and cardiometabolic risk factors, and median splits were used to define low/high (L/H) groups.

Results

Mean age was 76.7±3.2 years. Per decade of age, T/S ratio declined by 0.063 (p=0.0002), IGF-I by 18.4 ug/L (p<0.0001) and IGFBP3 by 467 ug/L (p<0.0001) while IGFBP1 increased by 12.1 ug/L (p<0.0001). IGF-I and IGFBP3 showed age-adjusted correlations with LTL (coefficient 0.059, p=0.001 and 0.045, p=0.013 respectively) IGFBP1 did not. In multivariable-adjusted models IGF-I and IGFBP3 (but not IGFBP1) were associated with LTL (estimated difference in T/S ratio 0.015 per 1SD increase in IGF-I, p=0.007 and 0.011 per 1SD increase in IGFBP3, p=0.049). Men with high IGF-I (>133 ug/L) and high estradiol (>70 pmol/L) (H/H) had longer LTL compared to men with low concentrations (L/L) (multivariable-adjusted T/S ratio H/H 1.20, p=0.007; H/L 1.18, p=0.147, L/H 1.16, p=0.877, L/L 1.16). There was no corresponding finding for IGF-I and testosterone.

Conclusions

Higher IGF-I and IGFBP3 are independently associated with longer telomeres, consistent with lower biological age, in older men. Additive influences of higher IGF-I and higher estradiol on telomere length are present. Further work is needed to clarify how hormonal exposures might interactively modulate biological ageing.

  1. Yeap BB, Knuiman MW, Divitini ML, Hui J, Arscott GM, Handelsman DJ, McLennan SV, Twigg SM, McQuillan B, Hung J, Beilby .P. Epidemiological and Mendelian randomisation studies of dihydrotestosterone and estradiol, and leucocyte telomere length in men. J Clin Endocrinol Metab 2016; 101: 1299-1306.
  2. Yeap BB, Hui J, Knuiman MW, Handelsman DJ, Flicker L, Divitini ML, Arscott GM, McLennan SV, Twigg SM, Almeida OP, Hankey GJ, Golledge J, Norman PE, Beilby JP. Cross-sectional associations of sex hormones with leucocyte telomere length, a marker of biological age, in a community-based cohort of older men. Clin Endocrinol 2019; 90: 562-569.