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Skeletal Muscle Gender Dimorphism from Proteomics
Published on: December 14, 2011
Gender-Specific Differences in Skeletal Muscle 11β-HSD1 Expression Across Healthy Aging
Zaki K Hassan-Smith1, Stuart A Morgan1, Mark Sherlock1
1Centre for Endocrinology, Diabetes, and Metabolism (Z.K.H.-S., S.A.M., B.H., A.E.T., G.G.L.), School of Clinical and Experimental Medicine, Institute for Biomedical Research, University of Birmingham, Edgbaston B15 2TT, United Kingdom; Department of Endocrinology (M.S.), Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland; Trinity College (M.S.), Dublin 2, Ireland; Oxford Centre for Diabetes, Endocrinology, and Metabolism (J.W.T.), University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LE, United Kingdom; and Faculty of Medicine and Health (P.M.S.), University of Leeds, Leeds LS2 9NL, United Kingdom.
Skeletal muscle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression increases with age in women, correlating with reduced grip strength and adverse metabolic markers. This suggests 11β-HSD1 inhibition as a potential strategy for age-related muscle decline.
Area of Science:
- Endocrinology
- Gerontology
- Muscle Physiology
Background:
- Cushing's syndrome shares body composition changes with aging, including sarcopenia, obesity, and osteoporosis.
- 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies local glucocorticoid activity by converting cortisone to cortisol.
- Age-related changes in body composition resemble those seen in Cushing's syndrome.
Purpose of the Study:
- To investigate the age-related expression and activity of 11β-HSD1 in human skeletal muscle.
- To identify potential causes for altered 11β-HSD1 activity with aging.
- To determine the consequences of age-related 11β-HSD1 changes on phenotypic markers of aging.
Main Methods:
- Cross-sectional observational study involving 134 healthy volunteers (aged 20-81 years).
- Assessment included body composition (DXA), muscle function (mechanography, grip strength), and skeletal muscle biopsies.
- Analysis of gene expression, urinary steroid profiles, and correlations between 11β-HSD1 activity and phenotypic/biochemical variables.
Main Results:
- Skeletal muscle 11β-HSD1 expression increased significantly with age in women (2.72-fold in >60 vs. 20-40 years), but not in men.
- Increased 11β-HSD1 expression in women correlated with age, reduced grip strength, higher body fat, insulin resistance, and altered lipid/hormone profiles.
- No age-related differences were found in 11β-HSD type 2, glucocorticoid receptor, or hexose-6-phosphate dehydrogenase expression, or in urinary steroid profiles.
Conclusions:
- Skeletal muscle 11β-HSD1 is upregulated with age in women, linked to diminished muscle strength and unfavorable metabolic/body composition profiles.
- These findings suggest that 11β-HSD1 plays a role in age-related muscle decline.
- Targeted inhibition of 11β-HSD1 may represent a therapeutic approach for mitigating age-related sarcopenia and associated conditions.
