Cross‐sectional associations of sex hormones with leucocyte telomere length, a marker of biological age, in a community‐based cohort of older men

Abstract

Context: Telomeres protect chromosomes from damage, and shorter leucocyte telomere length (LTL) is a marker of advancing biological age. The association between testosterone (T) and its bioactive metabolites, dihydrotestosterone (DHT) and oestradiol (E2) with telomere length, particularly in older men, is uncertain. The study aimed to clarify associations of sex hormones with LTL in older men. Participants and methods:We used cross-sectional data from 2913 men aged 76.7 ± 3.2 years with morning blood samples assayed for T, DHT, E2 (mass spectrometry), and sex hormone-binding globulin (SHBG, immunoassay), to correlate sex hormones with LTL measured using PCR and expressed as T/S ratio in multivariable linear regression models adjusted for age, cardiometabolic risk factors and cardiovascular disease history. Results: 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) and SHBG was inversely correlated (r = −0.053, P = 0.004). After multivariable adjustment, E2 was associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, P = 0.043), T and DHT were not associated.When E2 and SHBG were simultaneously included, E2 remained positively (coefficient 0.014, P = 0.014) and SHBG inversely (coefficient −0.013, P = 0.037) associated with T/S ratio. Conclusions:In older men, neither T nor DHT is associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated, thus relating sex hormone exposure to lower biological age. Further research is needed to determine causality and clarify the role of sex hormones in male ageing. K E Y W O R D Sageing male, androgen, biological age, leucocyte telomere length, oestrogen, sex hormonebinding globulin | 563 YEAP Et Al.

In utero exposure to chlordecone affects histone modifications and activates LINE-1 in cord blood

“…Estrogen-induced increased telomerase activity was demonstrated in several cell lines (54,55,56). Although telomerase activity is repressed in most somatic tissues, in highly proliferative tissues such as hematopoietic system, digestive system, and skin, TERT is still expressed (57), which makes possible the regulation of the TERT gene by estrogens (58).…”

Influence of cortisol awakening response on telomere length: Trends for males and females

“…Female testosterone levels are ten times lower than male's testosterone levels, conversely oestrogen levels in males are lower than females. Serum estradiol levels, the most potent form of oestrogen in reproductive aged women, have been positively correlated with leucocyte telomere length (Yeap et al., 2019). For post‐menopausal women, who experience a significant decline in estradiol levels, long‐term oestrogen therapy is associated with longer telomere lengths when compared to post‐menopausal women who have never taken hormone therapy (Lee et al., 2005).…”

Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone‐Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization

“…17 Additionally, it was observed that SHBG levels were independently and inversely correlated with LTL, suggesting that sex hormones may counteract the natural age-related decline in telomere length. 18,19 This association, particularly prominent among older individuals, highlights the potential role of sex hormones in preserving telomere integrity. 18 Multiple studies have shown that higher SHBG levels are related to a decline in BMD in both males and females, indicating a significant negative correlation between SHBG and osteoporosis.…”

“…A large population‐based cohort study has revealed a noticeable trend of increasing SHBG levels with advancing age 17 . Additionally, it was observed that SHBG levels were independently and inversely correlated with LTL, suggesting that sex hormones may counteract the natural age‐related decline in telomere length 18,19 . This association, particularly prominent among older individuals, highlights the potential role of sex hormones in preserving telomere integrity 18 .…”