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

• Unique study design of postmenopausal MZ twins discordant for HRT.
• Serum miR-21 and miR-146a levels 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 deteriorations.

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.