Mechanistic Links Underlying the Impact of C-Reactive Protein on Muscle Mass in ElderlyShow others and affiliations
2017 (English)In: Cellular Physiology and Biochemistry, ISSN 1015-8987, E-ISSN 1421-9778, Vol. 44, no 1, p. 267-278
Article in journal (Refereed) Published
Abstract [en]
BACKGROUND/AIMS: Mechanisms underlying the relationship between systemic inflammation and age-related decline in muscle mass are poorly defined. The purpose of this work was to investigate the relationship between the systemic inflammatory marker CRP and muscle mass in elderly and to identify mechanisms by which CRP mediates its effects on skeletal muscle, in-vitro.
METHODS: Muscle mass and serum CRP level were determined in a cohort of 118 older women (67±1.7 years). Human muscle cells were differentiated into myotubes and were exposed to CRP. The size of myotubes was determined after immunofluorescent staining using troponin. Muscle protein synthesis was assessed using stable isotope tracers and key signalling pathways controlling protein synthesis were determined using western-blotting.
RESULTS: We observed an inverse relationship between circulating CRP level and muscle mass (β= -0.646 (95% CI: -0.888, -0.405) p<0.05) and demonstrated a reduction (p < 0.05) in the size of human myotubes exposed to CRP for 72 h. We next showed that this morphological change was accompanied by a CRP-mediated reduction (p < 0.05) in muscle protein fractional synthetic rate of human myotubes exposed to CRP for 24 h. We also identified a CRP-mediated increased phosphorylation (p<0.05) of regulators of cellular energy stress including AMPK and downstream targets, raptor and ACC-β, together with decreased phosphorylation of Akt and rpS6, which are important factors controlling protein synthesis.
CONCLUSION: This work established for the first time mechanistic links by which chronic elevation of CRP can contribute to age-related decline in muscle function.
Place, publisher, year, edition, pages
Karger , 2017. Vol. 44, no 1, p. 267-278
Keywords [en]
Ageing; AMPK; Akt/mTOR; Chronic Inflammation; CRP; Myoblast; Protein Synthesis; Skeletal Muscle Cell; Old women
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Physiology
Identifiers
URN: urn:nbn:se:oru:diva-62772DOI: 10.1159/000484679ISI: 000423087200020PubMedID: 29130969Scopus ID: 2-s2.0-85033489852OAI: oai:DiVA.org:oru-62772DiVA, id: diva2:1159577
Note
Funding Agency:
Swedish National Center for Research in Sports P2012/0102 P2014-0117
2017-11-232017-11-232018-02-06Bibliographically approved
In thesis