title: Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy--a study with monozygotic twin pairs.
abstract: 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.
authors.affiliation: Gerontology Research Center, University of Jyväskylä, Finland; Department of Health Sciences, University of Jyväskylä, Finland. Electronic address: reeta.kangas@jyu.fi.
authors.forename: Reeta
authors.initials: R
authors.lastname: Kangas
authors.affiliation: Gerontology Research Center, University of Jyväskylä, Finland; Department of Health Sciences, University of Jyväskylä, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Pöllänen
authors.affiliation: Department of Clinical and Molecular Sciences, Division of Experimental Pathology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Rippo
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Via S. Giacomo, 12, University of Bologna, Bologna, Italy; Interdepartmental Center Galvani "CIG", Via Selmi, 3, University of Bologna, Bologna, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Lanzarini
authors.affiliation: Department of Clinical and Molecular Sciences, Division of Experimental Pathology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Prattichizzo
authors.affiliation: Department of Health Sciences, University of Jyväskylä, Finland.
authors.forename: Paula
authors.initials: P
authors.lastname: Niskala
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Finland; Gerontology Research Center, University of Tampere, Finland.
authors.forename: Juulia
authors.initials: J
authors.lastname: Jylhävä
authors.affiliation: Gerontology Research Center, University of Jyväskylä, Finland; Department of Health Sciences, University of Jyväskylä, Finland.
authors.forename: Sarianna
authors.initials: S
authors.lastname: Sipilä
authors.affiliation: Institute for Molecular Medicine, University of Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Department of Clinical and Molecular Sciences, Division of Experimental Pathology, Università Politecnica delle Marche, Ancona, Italy; Department of Clinical Pathology and Innovative Therapy, Advanced Technology Center for Aging Research, INRCA-IRCCS, Ancona, Italy.
authors.forename: Antonio Domenico
authors.initials: AD
authors.lastname: Procopio
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Via S. Giacomo, 12, University of Bologna, Bologna, Italy; Interdepartmental Center Galvani "CIG", Via Selmi, 3, University of Bologna, Bologna, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Via S. Giacomo, 12, University of Bologna, Bologna, Italy; Interdepartmental Center Galvani "CIG", Via Selmi, 3, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Clinical and Molecular Sciences, Division of Experimental Pathology, Università Politecnica delle Marche, Ancona, Italy; Department of Clinical Pathology and Innovative Therapy, Advanced Technology Center for Aging Research, INRCA-IRCCS, Ancona, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Olivieri
authors.affiliation: Gerontology Research Center, University of Jyväskylä, Finland; Department of Health Sciences, University of Jyväskylä, Finland.
authors.forename: Vuokko
authors.initials: V
authors.lastname: Kovanen
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D015914:Estrogen Replacement Therapy / Q000379:methods; D004967:Estrogens / Q000008:administration & dosage*; D053222:Fas Ligand Protein / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D035683:MicroRNAs / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D017698:Postmenopause / Q000097:blood / Q000235:genetics / Q000502:physiology; D014430:Twins, Monozygotic
chemical_list: D015415:Biomarkers; D004967:Estrogens; D053222:Fas Ligand Protein; D035683:MicroRNAs
keywords: Apoptosis; Estrogen; Hormone replacement therapy; Micrornas; “Inflamm-aging”