The aim is to improve understanding of detailed molecular and physiological mechanisms responsible for the maintenance of healthy muscles with advancing age in women more prone to age-related muscle wasting and associated problems than same age men. We investigate the effects of and associations with estrogen-based hormone replacement therapy (HRT) and muscle characteristics and body composition in postmenopausal women in order to explore estrogen and other steroid hormones as molecular mechanism for aging-induced muscle weakness. Especially the muscle-fat cross-talk will be in focus.
Study subjects include both pre- and postmenopausal women as well as identical postmenopausal twin pairs discordant for HRT i.e. the other twin uses HRT for several years while the co-twin has never used HRT. Body composition, muscle-related phenotype data, as well as muscle, adipose tissue and blood samples (whole blood, serum, plasma, leukocytes) are available from the women. In addition to conventional cell and molecular biological and biochemical analyses also high through-put techniques like gene expression arrays, miRNA arrays, epigenomic, proteomic and metabonomic analyses are done or ongoing.
Research collaboration within this study entity includes Finnish researchers at Universities Helsinki, Oulu, Kuopio and Jyväskylä and internationally at Universities Uppsala, Padova, Ancona and Paris via MYOAGE and ENGAGE research consortia (EU/FP7). The HRT specific knowledge, both in relation to sarcopenia and other health outcomes will add our understanding, when evaluating the possible positive and negative effects of HRT. This study will increase our knowledge of the genetic and molecular mechanisms behind sarcopenia and responsiveness to interventions upon aging. Consequently, the results are crucial for developing rational preventive and therapeutic measures and interventions for old age disability, which can be applied e.g. at health and rehabilitation centers.
Finnish Ministry of Culture and Education, Academy of Finland, MYOAGE
Adjunct professor, PhD Vuokko Kovanen, Department of Health Sciences, University of Jyväskylä
- Laakkonen EK, Soliymani R, Karvinen S, Kaprio J, Kujala UM, Baumann M, Sipilä S, Kovanen V, Lalowski M. Estrogenic regulation of skeletal muscle proteome: a study of premenopausal women and postmenopausal MZ cotwins discordant for hormonal therapy. Aging Cell., 16(6):1276-1287 2017.
- Sillanpää E, Niskala P, Laakkonen EK, Ponsot E, Alén M, Kaprio J, Kadi F, Kovanen V, Sipilä S. Leukocyte and Skeletal Muscle Telomere Length and Body Composition in Monozygotic Twin Pairs Discordant for Long-term Hormone Replacement Therapy. Twin Res Hum Genet. 20(2):119-131. 2017.
- Bahl A, Pöllänen E, Ismail K, Sipilä S, Mikkola TM, Berglund E, Lindqvist CM, Syvänen AC, Rantanen T, Kaprio J, Kovanen V, Ollikainen M. Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass. Twin Res Hum Genet. 18(6):647-61. 2015.
- Sipilä S, Finni T, Kovanen V. Estrogen influences on neuromuscular function in postmenopausal women. Calcif Tissue Int. 96(3):222-33. 2015.
- Olivieri F, Ahtiainen M, Lazzarini R, Pöllänen E, Capri M, Lorenzi M, Fulgenzi G, Albertini MC, Salvioli S, Alen MJ, Kujala UM, Borghetti G, Babini L, Kaprio J, Sipilä S, Franceschi C, Kovanen V, Procopio AD. Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-223 expressions: a study on postmenopausal monozygotic twin pairs. Aging Cell. 13(5):850-61. 2014.
- Toivonen MH, Pöllänen E, Ahtiainen M, Suominen H, Taaffe DR, Cheng S, Takala T, Kujala UM, Tammi MI, Sipilä S, Kovanen V.OGT and OGA expression in postmenopausal skeletal muscle associates with hormone replacement therapy and muscle cross-sectional area. Exp Gerontol. 48(12):1501-4. 2013.
- Sipilä S, Narici M, Kjaer M, Pöllänen E, Atkinson RA, Hansen M, Kovanen V. Sex hormones and skeletal muscle weakness. Biogerontology. 14(3):231-45. 2013.
- Qaisar R, Renaud G, Hedstrom Y, Pöllänen E, Ronkainen P, Kaprio J, Alen M, Sipilä S, Artemenko K, Bergquist J, Kovanen V, Larsson L. Hormone replacement therapy improves contractile function and myonuclear organization of single muscle fibres from postmenopausal monozygotic female twin pairs. J Physiol. 1; 591(Pt 9):2333-44. 2013.
- Ahtiainen M, Pöllänen E, Ronkainen PH, Alén M, Puolakka J, Kaprio J, Sipilä S, Kovanen V. Age and estrogen-based hormone therapy affect systemic and local IL-6 and IGF-1 pathways in women. AGE 34(5):1249-1260. 2012.
- Ahtiainen, M, Alén M, Pöllänen E, Pulkkinen S, Ronkainen PH, Kujala UM, Kaprio J, Sipilä S, Kovanen V. Hormone therapy is associated with better body composition and adipokine/glucose profiles: a study with monozygotic co-twin control design. Menopause 19 (12):1329.-35. 2012.
- Finni T, Noorkoiv M, Pöllänen E, Ronkainen PH, Alén M, Kaprio J, Kovanen V, Sipilä S. 2011. Muscle function in monozygotic female twin pairs discordant for hormone replacement therapy. Muscle Nerve. 44(5):769-75. 2011.
- Mikkola TM, Heinonen A, Kovanen V, Cheng S, Kujala UM, Suominen H, Alén M, Puolakka J, Ankarberg-Lindgren C, Ronkainen PH, Koskenvuo M, Kaprio J, Rantanen T, Sipilä S. Influence of long-term postmenopausal hormone replacement therapy on estimated structural bone strength: A study in discordant monozygotic twins. J Bone Miner Res. 26(3):546-52. 2011
University of Helsinki (Jaakko Kaprio)
University of Eastern Finland (Markku Tammi)
University of Oulu (Mika Ala-Korpela)
University of Bologna, Italy (Claudio Franceschi)
Univesrsity of Ancona, Italy (Antonio Procopio)
University of Uppsala, Sweden (Lars Larsson)
ENGAGE- consortio (EU/FP7)
University of Helsinki (Jaakko Kaprio)
University of Uppsala, Sweden (Ann-Christine Syvänen)