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
European Journal of Endocrinology 2019 October 1

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.

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