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Mechanistic Links Underlying the Impact of C-Reactive Protein on Muscle Mass in Elderly
Örebro University, School of Health Sciences.
MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom.
Örebro University, School of Health Sciences.
School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
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2017 (English)In: Cellular Physiology and Biochemistry, ISSN 1015-8987, E-ISSN 1421-9778, Vol. 44, no 1, 267-278 p.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, 267-278 p.
Keyword [en]
AMPK, Ageing, Akt/mTOR, CRP, Chronic Inflammation, Myoblast, Old women, Protein Synthesis, Skeletal Muscle Cell
National Category
Sport and Fitness Sciences
Identifiers
URN: urn:nbn:se:oru:diva-62772DOI: 10.1159/000484679PubMedID: 29130969Scopus ID: 2-s2.0-85033489852OAI: oai:DiVA.org:oru-62772DiVA: diva2:1159577
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Skeletal Muscle Mass & Function in Older Women: Health-Enhancing Influences of Combined Resistance Exercise & Diet
Open this publication in new window or tab >>Skeletal Muscle Mass & Function in Older Women: Health-Enhancing Influences of Combined Resistance Exercise & Diet
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ageing is accompanied by a progressive decline in skeletal muscle mass and strength which may lead to impaired ability to perform activities of daily living in older adults. Although the exact cause of the gradual decline in muscle mass is unknown, identifying efficient strategies aiming to prevent age-related loss of muscle mass and strength is important in order to promote healthy ageing. The overall aim of this thesis was to explore the effects of resistance training alone or combined with a healthy diet on skeletal muscle mass and function of healthy recreationally active older women and to determine mechanisms by which elevated systemic inflammation may contribute to the age-related decline of muscle mass in older adults. The combination of resistance training and a healthy diet induced gains in leg lean mass as well as greater gains in dynamic explosive force than resistance training alone in healthy recreationally active older women. The observed gains in leg lean mass were accompanied by increases in the size of type IIA muscle fibres together with down-regulation in gene expression of a pro-inflammatory factor (IL-1β) and upregulation in gene expression of a regulator of cellular growth (mTOR) in skeletal muscle of older women. Additionally, reduced muscle protein synthesis and size of muscle cells may mediate the detrimental effects of elevated circulating markers of inflammation on muscle mass in older adults. In conclusion, the present thesis depicts mechanistic links between elevated systemic marker of inflammation and muscle mass and provides new information on the effects of combined resistance training and healthy diet on muscle mass and strength in a group of healthy recreationally active older women. This knowledge is instrumental for development of strategies aiming to prevent age-related loss of muscle mass and function.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2017. 79 p.
Series
Örebro Studies in Sport Sciences, ISSN 1654-7535 ; 26
Keyword
Healthy ageing, Chronic inflammation, C-reactive protein, Omega-3 fatty acids, Resistance training, Physical function
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:oru:diva-61234 (URN)978-91-7529-218-2 (ISBN)
Public defence
2017-12-12, Örebro universitet, Hörsal G, Gymnastikhuset, Fakultetsgatan 1, Örebro, 09:00 (Swedish)
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Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2017-11-23Bibliographically approved

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Wåhlin-Larsson, BrittaStrandberg, EmelieKadi, Fawzi

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