Increased skeletal muscle 11βHSD1 mRNA is associated with lower muscle strength in ageing

Kilgour, A. H.M. et al. (2013) Increased skeletal muscle 11βHSD1 mRNA is associated with lower muscle strength in ageing. PLoS ONE, 8(12), e84057. (doi:10.1371/journal.pone.0084057) (PMID:24391882) (PMCID:PMC3877148)

[img]
Preview
Text
90514.pdf - Published Version
Available under License Creative Commons Attribution.

174kB

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 (11βHSD1) 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 11βHSD1 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 5β-tetrahydrocortisol +5α-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11βHSD activity). Muscle strength was associated with 11βHSD1 mRNA levels (β -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 11βHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11βHSD1 may have therapeutic potential in sarcopenia.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Husi, Dr Holger
Authors: 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., and Greig, C. A.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
First Published:First published in PLoS ONE 8(12):e84057
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record