Increased skeletal muscle 11betaHSD1 mRNA is associated with lower muscle strength in ageing

Alixe H.M. Kilgour, Iain J. Gallagher, Alasdair M.J. Maclullich, Ruth Andrew, Calum D. Gray, Philippa Hyde, Henning Wackerhage, Holger Husi, James A. Ross, John M. Starr, Karen E. Chapman, Kenneth C.H. Fearon, Brian R. Walker, Carolyn A. Greig

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Abstract

Background: Sarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC) in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR) signaling by increased expression of either GR or the GC-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in muscle. Methods: There were 82 participants; group 1 comprised 33 older men (mean age 70.2years, SD 4.4) and 19 younger men (22.2years, 1.7) and group 2 comprised 16 older men (79.1years, 3.4) and 14 older women (80.1years, 3.7). We measured muscle strength, mid-thigh cross-sectional area, fasting morning plasma cortisol, quadriceps muscle GR and 11betaHSD1 mRNA, and urinary glucocorticoid metabolites. Data were analysed using multiple linear regression adjusting for age, gender and body size. Results: Muscle strength and size were not associated with plasma cortisol, total urinary glucocorticoids or the ratio of urinary 5beta-tetrahydrocortisol +5alpha-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11betaHSD activity). Muscle strength was associated with 11betaHSD1 mRNA levels (beta -0.35, p = 0.04), but GR mRNA levels were not significantly associated with muscle strength or size. Conclusion: Although circulating levels of GC are not associated with muscle strength or size in either gender, increased cortisol generation within muscle by 11betaHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11betaHSD1 may have therapeutic potential in sarcopenia.
Original languageEnglish
Pages (from-to)e84057
JournalPLoS ONE
Volume8
Issue number12
DOIs
Publication statusPublished - 2013

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    Kilgour, A. H. M., Gallagher, I. J., Maclullich, A. M. J., Andrew, R., Gray, C. D., Hyde, P., Wackerhage, H., Husi, H., Ross, J. A., Starr, J. M., Chapman, K. E., Fearon, K. C. H., Walker, B. R., & Greig, C. A. (2013). Increased skeletal muscle 11betaHSD1 mRNA is associated with lower muscle strength in ageing. PLoS ONE, 8(12), e84057. https://doi.org/10.1371/journal.pone.0084057