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Age and estrogen-based hormone therapy affect systemic and local IL-6 and IGF-1 pathways in women

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Abstract

A thorough understanding of the role of estrogens on aging-related muscle weakness is lacking. To clarify the molecular mechanisms underlying the effects of hormone replacement therapy (HRT) on skeletal muscle, we analyzed systemic protein and local mRNA levels of factors related to interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) pathways in 30- to 35-year-old (n = 14) women (without hormonal contraceptives) and in 54- to 62-year-old monozygotic female twin pairs discordant for HRT (n = 11 pairs, mean duration of HRT 7.3 ± 3.7 years). Biopsies were taken from vastus lateralis muscle and from abdominal adipose tissue. We found, first, that the systemic levels of IL-6 receptors sIL-6R and sgp130 are sensitive to both age and HRT concomitant with the changes in body composition. The serum levels of sgp130 and sIL-6R were 16% and 52% (p ≤ 0.001 for both variables) higher in postmenopausal women than in premenopausal women, and 10% and 9% lower (p = 0.033 and p < 0.001, respectively) in the HRT using than in their non using co-twins. After adjustment for body fat amount, the differences were no more significant. Second, the transcript analyses emphasize the impact of adipose tissue on systemic levels of IL-6, sgp130 and sIL6R, both at pre- and postmenopausal age. In muscle, the most notable changes were 28% lower gene expression of IGF-1 splice variant Ea (IGF-1Ea) and 40% lower expression of splice variant Ec (IGF-1Ec) in the postmenopausal non-users than in premenopausal women (p = 0.016 and 0.019, respectively), and 28% higher expression of IGF1-receptor in HRT users than in non-users (p = 0.060). The results tend to demonstrate that HRT has positive anti-catabolic effect on aging skeletal muscle.

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Acknowledgements

We acknowledge the support from the Academy of Finland, Finnish Ministry of Education and the EC FP7 Collaborative Project MYOAGE (GA-223576).

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Authors and Affiliations

  1. Gerontology Research Center, Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland

    Maarit Ahtiainen, Eija Pöllänen, Paula H. A. Ronkainen, Sarianna Sipilä & Vuokko Kovanen

  2. Department of Medical Rehabilitation, Oulu University Hospital and Institute of Health Sciences, University of Oulu, Oulu, Finland

    Markku Alen

  3. Central Finland Central Hospital, Jyväskylä, Finland

    Jukka Puolakka

  4. Department of Public Health, Institute for Molecular Medicine, University of Helsinki, National Institute for Health and Welfare, Helsinki, Finland

    Jaakko Kaprio

  5. Department of Health Sciences, University of Jyväskylä, P.O. Box 35 (Viveca 283), 40014, Jyväskylä, Finland

    Maarit Ahtiainen

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  1. Maarit Ahtiainen
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Correspondence to Maarit Ahtiainen.

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Ahtiainen, M., Pöllänen, E., Ronkainen, P.H.A. et al. Age and estrogen-based hormone therapy affect systemic and local IL-6 and IGF-1 pathways in women. AGE 34, 1249–1260 (2012). https://doi.org/10.1007/s11357-011-9298-1

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