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

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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.peerReviewe

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 and its’ remodeling, which are partly due to changes in the hormonal profile. MicroRNAs are known to post-transcriptionally regulate various cellular processes associated with cell senescence; differentiation, replication and apoptosis. Measured from the serum, microRNAs have the 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 tissue biopsy samples obtained from 54-62 year-old postmenopausal monozygotic twins (n=11 pairs) discordant for the use of HRT. Premenopausal 30-35 year-old women (n=8) were used as young controls. We focused on the hormonal aging and more specifically, on the interaction between HRT use and the modulation of inflammation associated microRNAs, miR-21 and miR-146a, and classical inflammation markers. Fas-ligand (FasL) was analysed since it functions in both apoptosis and inflammation. The inflammatory profile is healthier among the premenopausal women compared to the older, postmenopausal twins. The serum miR-21 and miR-146a expression levels and FasL concentrations were lower in the HRT users when compared to their non-using co-twins, demonstrating their responsiveness to HRT. Based on the pairwise FasL analysis, the FasL serum concentration is likely to be genetically controlled. Overall, we suggest that postmenopausal estrogen deficiency sustains the development of “inflamm-aging” in women. Estrogen sensitive, specific circulating microRNAs could be potential, early biomarkers for age-associated physiological deteriorations. Highlights: Unique study design of postmenopausal MZ twins discordant for HRT Serum miR-21 and miR-146a expressions are lower in HRT users compared to non-users FasL serum concentrations are lower in HRT users and possibly genetically regulated Postmenopausal systemic estrogen deficiency partly contributes to the “inflamm-aging” Serum miR-21/-146a early indicators of age-associated physiological deteriorationspeerReviewe