Leukocyte and Skeletal Muscle Telomere Length and Body Composition in Monozygotic Twin Pairs Discordant for Long-term Hormone Replacement Therapy.

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r = 0.69, p = .020) and in mean (r = 0.74, p = .014) and minimum SMTL (r = 0.88, p = .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r 2 = 0.30, p = .030), percentage total body (r 2 = 0.43, p = .014), and thigh (r 2 = 0.55, p = .004) fat, while minimum SMTL was associated with fat-free mass (r 2 = 0.27, p = .020) and thigh muscle area (r 2 = 0.42, p = .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.

Intramuscular sex steroid hormones are associated with skeletal muscle strength and power in women with different hormonal status.

Estrogen (E2 )-responsive peripheral tissues, such as skeletal muscle, may suffer from hormone deficiency after menopause potentially contributing to the aging of muscle. However, recently E2 was shown to be synthesized by muscle and its systemic and intramuscular hormone levels are unequal. The objective of the study was to examine the association between intramuscular steroid hormones and muscle characteristics in premenopausal women (n = 8) and in postmenopausal monozygotic twin sister pairs (n = 16 co-twins from eight pairs) discordant for the use of E2 -based hormone replacement. Isometric skeletal muscle strength was assessed by measuring knee extension strength. Explosive lower body muscle power was assessed as vertical jump height. Due to sequential nature of enzymatic conversion of biologically inactive dehydroepiandrosterone (DHEA) to testosterone (T) and subsequently to E2 or dihydrotestosterone (DHT), separate linear regression models were used to estimate the association of each hormone with muscle characteristics. Intramuscular E2 , T, DHT, and DHEA proved to be significant, independent predictors of strength and power explaining 59-64% of the variation in knee extension strength and 80-83% of the variation of vertical jumping height in women (P < 0.005 for all models). The models were adjusted for age, systemic E2 , and total body fat mass. The statistics used took into account the lack of statistical independence of twin sisters. Furthermore, muscle cells were shown to take up and actively synthesize hormones. Present study suggests intramuscular sex steroids to associate with strength and power regulation in female muscle providing novel insight to the field of muscle aging.

Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy--a study with monozygotic twin pairs.

Biological aging is associated with physiological deteriorations, which are partly due to changes in the hormonal profile. MicroRNAs regulate various processes associated with cell senescence; differentiation, replication and apoptosis. Serum microRNAs have potential to serve as noninvasive markers for diagnostics/prognostics and therapeutic targets. We analysed the association of estrogen-based hormone replacement therapy (HRT) with selected microRNAs and inflammation markers from the serum, leukocytes and muscle biopsy samples from 54 to 62 year-old postmenopausal monozygotic twins (n=11 pairs) discordant for HRT usage. Premenopausal 30-35 year-old women (n=8) were used as young controls. We focused on the hormonal aging and on the interaction between HRT use and the modulation of miR-21, miR-146a and classical inflammation markers. Fas-ligand was analysed since it functions in both apoptosis and inflammation. The inflammatory profile was healthier among the premenopausal women compared to the postmenopausal twins. Serum miR-21 and miR-146a levels and FasL concentrations were lower in HRT users compared to their non-using co-twins, demonstrating their responsiveness to HRT. Based on the pairwise FasL analysis, FasL concentration is likely to be genetically controlled. Overall, we suggest that postmenopausal estrogen deficiency sustains the development of "inflamm-aging". Estrogen sensitive, specific circulating microRNAs could be potential, early biomarkers for age-associated physiological deteriorations.