title: Increased skeletal muscle 11βHSD1 mRNA is associated with lower muscle strength in ageing.
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 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) in muscle.
  
  
  METHODS
  There were 82 participants; group 1 comprised 33 older men (mean age 70.2 years, SD 4.4) and 19 younger men (22.2 years, 1.7) and group 2 comprised 16 older men (79.1 years, 3.4) and 14 older women (80.1 years, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, Geriatric Medicine Unit, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alixe H M
authors.initials: AH
authors.lastname: Kilgour
authors.affiliation: Department of Clinical and Surgical Sciences, Division of Health Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Gallagher
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, Geriatric Medicine Unit, University of Edinburgh, Edinburgh, United Kingdom ; Department of Clinical and Surgical Sciences, Division of Health Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alasdair M J
authors.initials: AM
authors.lastname: MacLullich
authors.affiliation: Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.affiliation: Clinical Research Imaging Centre, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Calum D
authors.initials: CD
authors.lastname: Gray
authors.affiliation: Department of Clinical and Surgical Sciences, Division of Health Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Philippa
authors.initials: P
authors.lastname: Hyde
authors.affiliation: School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Henning
authors.initials: H
authors.lastname: Wackerhage
authors.affiliation: Department of Clinical and Surgical Sciences, Division of Health Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Holger
authors.initials: H
authors.lastname: Husi
authors.affiliation: Department of Clinical and Surgical Sciences, Division of Health Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, Geriatric Medicine Unit, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.affiliation: Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Chapman
authors.affiliation: Department of Clinical and Surgical Sciences, Division of Health Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Kenneth C H
authors.initials: KC
authors.lastname: Fearon
authors.affiliation: Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: Department of Clinical and Surgical Sciences, Division of Health Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Greig
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005938:Glucocorticoids / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007118:Immunoassay; D008297:Male; D053580:Muscle Strength / Q000502:physiology*; D018908:Muscle Weakness / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D006854:Hydrocortisone