title: Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy.
abstract: Exosomes participate in intercellular messaging by transporting bioactive lipid-, protein- and RNA-molecules and -complexes. The contents of the exosomes reflect the physiological status of an individual making exosomes promising targets for biomarker analyses. In the present study we extracted exosome microRNAs (exomiRs) from serum samples of premenopausal women (n = 8) and monozygotic postmenopausal twins (n = 10 female pairs), discordant for the use of estrogenic hormone replacement therapy (HRT), in order to see whether the age or/and the use of HRT associates with exomiR content. A total of 241 exomiRs were detected by next generation sequencing, 10 showing age, 14 HRT and 10 age +HRT -related differences. When comparing the groups, differentially expressed miRs were predicted to affect cell proliferation processes showing inactivation with younger age and HRT usage. MiR-106-5p, -148a-3p, -27-3p, -126-5p, -28-3p and -30a-5p were significantly associated with serum 17β-estradiol. MiRs formed two hierarchical clusters being indicative of positive or negative health outcomes involving associations with body composition, serum 17β-estradiol, fat-, glucose- and inflammatory markers. Circulating exomiR clusters, obtained by NGS, could be used as indicators of metabolic and inflammatory status affected by hormonal changes at menopause. Furthermore, the individual effects of HRT-usage could be evaluated based on the serum exomiR signature.
authors.affiliation: Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Reeta
authors.initials: R
authors.lastname: Kangas
authors.affiliation: Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Törmäkangas
authors.affiliation: Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Vidal
authors.initials: V
authors.lastname: Fey
authors.affiliation: Turku Clinical Sequencing Laboratory, University of Turku, Turku, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Pursiheimo
authors.affiliation: Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Miinalainen
authors.affiliation: Department of Medical Rehabilitation, Oulu University Hospital, Oulu, Finland.|Center for Life Course Health Research, University of Oulu, Oulu, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Alen
authors.affiliation: National Institute for Health and Welfare, University of Helsinki, Helsinki, Finland.|Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Sarianna
authors.initials: S
authors.lastname: Sipilä
authors.affiliation: Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Anna-Marja
authors.initials: AM
authors.lastname: Säämänen
authors.affiliation: Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Vuokko
authors.initials: V
authors.lastname: Kovanen
authors.affiliation: Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Eija K
authors.initials: EK
authors.lastname: Laakkonen
mesh_terms: D000328:Adult; D015415:Biomarkers; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D004958:Estradiol