dc.contributor.author | Kangas, Reeta | |
dc.date.accessioned | 2018-01-16T13:02:23Z | |
dc.date.available | 2018-01-16T13:02:23Z | |
dc.date.issued | 2018 | |
dc.identifier.isbn | 978-951-39-7324-7 | |
dc.identifier.other | oai:jykdok.linneanet.fi:1814700 | |
dc.identifier.uri | https://jyx.jyu.fi/handle/123456789/56753 | |
dc.description.abstract | This thesis took an innovative approach, which involved methodological development, to
investigate microRNAs as candidate molecules and as genome-wide regulators of age,
menopausal status and physical condition in both sexes. The focus was on potential serum
microRNAs indicative of age, pre- or postmenopausal status, with or without estrogen-
based hormone replacement therapy (HRT), and long-term physical training. MicroRNA
associations with adiposity and inflammatory markers were also analyzed.
Three different study designs were used: 1) the SAWEs study comprised healthy
postmenopausal monozygotic twin sisters (n=11, 54-62 years) with discordance for HRT
and premenopausal women (n=30, 20-40 years) without hormonal contraceptives; 2) the
miRBody study comprised non-related postmenopausal women (54-62 years) either on
(n=16) or not on HRT (n=17); and 3) the ATHLAS study comprised male masters sprinters
in a 10-year follow-up design (n=49, baseline age 40-80 years) and in a cross-sectional
design (n=67, 18-90 years). For the explorative microRNA discovery, we set up next
generation sequencing method for serum exosome microRNAs, exomiRs, and utilized
arrays for freely circulating serum and adipose tissue microRNAs. Selected microRNAs
were further validated. MiR-21-5p and -146a-5p were analyzed in both sexes, owing to
their hypothesized role in aging, inflammation and exercise response. Sex steroids,
inflammatory markers and fat/glucose metabolites were measured.
Profiled microRNA patterns in serum and adipose tissue differed by age and HRT
use vs. non-use. Validations revealed age associations for five, and HRT associations for
three microRNAs in serum. In addition, seven adipose tissue microRNAs were higher with
higher ages. MiR-146a-5p was negatively associated with HRT use in both serum and
muscle. In the sprinters, a negative association with age was detected for serum miR-146a-
5p and non-linear associations with specific power and speed capacity measures in 10 years
for miR-146a-5p and -21-5p.
The depth of the methodologies and human designs used, enabled novel discoveries
regarding aging, 17ǃ-estradiol (E2), and physiological (health) status-associated
microRNAs. Of them, exomiR-27b-3p and -148a-5p, indicative of higher age, lower serum
E2 and poorer adiposity and inflammatory status in women, were the most promising
candidates for early markers of worsening metabolism with declining systemic E2.
Moreover, serum miR-21-5p was indicative of more inflamed and fatty phenotype in
women, whereas miR-146a-5p appeared indicative of a healthier phenotype in both sexes.
Overall, this research underlines the potential for using serum microRNAs, together with
other traditional markers, as tools in evaluating the physiological status of an individual,
thus contributing new information to the health and aging field. | |
dc.format.extent | 1 verkkoaineisto (109 sivua, 36 sivua useina numerointijaksoina, 3 numeroimatonta sivua) : kuvitettu | |
dc.language.iso | eng | |
dc.publisher | University of Jyväskylä | |
dc.relation.ispartofseries | Studies in sport, physical education and health | |
dc.relation.haspart | <b>Artikkeli I:</b> Kangas R, Törmäkangas T, Fey V, Pursiheimo J, Miinalainen I, Alen M,
Kaprio J, Sipilä S, Säämänen A-M, Kovanen V, Laakkonen EK. 2017. Aging
and serum exomiR content in women -effects of estrogenic hormone
replacement therapy. Scientific Reports. 14;7:42702. </i><a href=" http://dx.doi.org/110.1038/srep42702"target="_blank"> DOI: 10.1038/srep42702.</a> | |
dc.relation.haspart | <b>Artikkeli II:</b> Kangas R, Morsiani C, Pizza G, Lanzarini C, Aukee P, Kaprio J, Sipilä S,
Franceschi C, Kovanen V, Laakkonen EK, Capri M. 2017. Menopausal
status associates with specific microRNA and target expressions in subcutaneous
adipose tissue. <i>Submitted manuscript. </i> | |
dc.relation.haspart | <b>Artikkeli III:</b> Kangas R, Pöllänen E, Rippo MR, Lanzarini C, Prattichizzo F, Niskala P,
Jylhävä J, Sipilä S, Kaprio J, Procopio AD, Capri M, Franceschi C, Olivieri
F, Kovanen V. 2014. Circulating miR-21, miR-146a and Fas ligand respond
to postmenopausal estrogen-based hormone replacement therapy
– a study with monozygotic twin pairs. Mechanisms of Ageing and Development.
15;143-144:1-8.
</i><a href=" http://dx.doi.org/10.1016/j.mad.2014.11.001
"target="_blank"> DOI: 10.1016/j.mad.2014.11.001.</a> | |
dc.relation.haspart | <b>Artikkeli IV:</b> Kangas R, Törmäkangas T, Heinonen A, Alen M, Suominen H, Kovanen
V, Laakkonen EK, Korhonen MT. 2017. Declining physical performance
associates with serum FasL, miR-21, and miR-146a in aging sprinters. Biomed
Research International. </i><a href=" https://doi.org/10.1155/2017/8468469"target="_blank"> DOI: 10.1155/2017/8468469.</a> | |
dc.relation.isversionof | Yhteenveto-osa ja 4 eripainosta julkaistu myös painettuna. | |
dc.rights | In Copyright | |
dc.subject.other | microRNA | |
dc.subject.other | serum | |
dc.subject.other | aging | |
dc.subject.other | estrogen | |
dc.subject.other | hormone replacement therapy | |
dc.subject.other | menopause | |
dc.subject.other | physical performance | |
dc.title | Aging and microRNA messaging : associations with systemic estrogen levels and physical performance | |
dc.type | Diss. | |
dc.identifier.urn | URN:ISBN:978-951-39-7324-7 | |
dc.type.dcmitype | Text | en |
dc.type.ontasot | Väitöskirja | fi |
dc.type.ontasot | Doctoral dissertation | en |
dc.contributor.tiedekunta | Liikuntatieteellinen tiedekunta | fi |
dc.contributor.yliopisto | University of Jyväskylä | en |
dc.contributor.yliopisto | Jyväskylän yliopisto | fi |
dc.contributor.oppiaine | Gerontologia ja kansanterveys | fi |
dc.relation.issn | 0356-1070 | |
dc.relation.numberinseries | 267 | |
dc.rights.accesslevel | openAccess | |
dc.subject.yso | mikro-RNA | |
dc.subject.yso | seerumi | |
dc.subject.yso | ikääntyminen | |
dc.subject.yso | estrogeenit | |
dc.subject.yso | hormonihoito | |
dc.subject.yso | vaihdevuodet | |
dc.subject.yso | suorituskyky | |
dc.subject.yso | gerontologia | |
dc.rights.url | https://rightsstatements.org/page/InC/1.0/ | |