title: Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults.
abstract: Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and pro-inflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ∼4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest (P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1β, were elevated in serum samples following bed rest (P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness.
authors.affiliation: Univ. of Utah, 520 Wakara Way, Salt Lake City, UT 84108-1213, USA. micah.drummond@hsc.utah.edu
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Drummond
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Timmerman
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Markofski
authors.forename: Dillon K
authors.initials: DK
authors.lastname: Walker
authors.forename: Jared M
authors.initials: JM
authors.lastname: Dickinson
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jamaluddin
authors.forename: Allan R
authors.initials: AR
authors.lastname: Brasier
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
mesh_terms: D000368:Aged; D045930:Anabolic Agents / Q000494:pharmacology; D001284:Atrophy; D001510:Bed Rest / Q000009:adverse effects*; D001706:Biopsy; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*
chemical_list: D045930:Anabolic Agents; D016207:Cytokines; D018076:DNA, Complementary; D015850:Interleukin-6; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D012313:RNA
keywords: aging; atrophy; cytokine; hospitalization; physical inactivity