Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults

Todd A. Trappe, Robert A. Standley, Bozena Jemiolo, Chad C. Carroll, Scott W. Trappe


Twelve weeks of resistance training (3 days/wk) combined with daily consumption of the cyclooxygenase-inhibiting drugs acetaminophen (4.0 g/day; n = 11, 64 ± 1 yr) or ibuprofen (1.2 g/day; n = 13, 64 ± 1 yr) unexpectedly promoted muscle mass and strength gains 25–50% above placebo (n = 12, 67 ± 2 yr). To investigate the mechanism of this adaptation, muscle biopsies obtained before and ∼72 h after the last training bout were analyzed for mRNA levels of prostaglandin (PG)/cyclooxygenase pathway enzymes and receptors [arachidonic acid synthesis: cytosolic phospholipase A2 (cPLA2) and secreted phospholipase A2 (sPLA2); PGF synthesis: PGF synthase and PGE2 to PGF reductase; PGE2 synthesis: PGE2 synthase-1, -2, and -3; PGF receptor and PGE2 receptor-4], cytokines and myokines involved in skeletal muscle adaptation (TNF-α, IL-1β, IL-6, IL-8, IL-10), and regulators of muscle growth [myogenin, myogenic regulatory factor-4 (MRF4), myostatin] and atrophy [Forkhead box O3A (FOXO3A), atrogin-1, muscle RING finger protein 1 (MuRF-1), inhibitory κB kinase β (IKKβ)]. Training increased (P < 0.05) cPLA2, PGF synthase, PGE2 to PGF reductase, PGE2 receptor-4, TNF-α, IL-1β, IL-8, and IKKβ. However, the PGF receptor was upregulated (P < 0.05) only in the drug groups, and the placebo group upregulation (P < 0.05) of IL-6, IL-10, and MuRF-1 was eliminated in both drug groups. These results highlight prostaglandin and myokine involvement in the adaptive response to exercise in older individuals and suggest two mechanisms underlying the enhanced muscle mass gains in the drug groups: 1) The drug-induced PGF receptor upregulation helped offset the drug suppression of PGF-stimulated protein synthesis after each exercise bout and enhanced skeletal muscle sensitivity to this stimulation. 2) The drug-induced suppression of intramuscular PGE2 production increased net muscle protein balance after each exercise bout through a reduction in PGE2-induced IL-6 and MuRF-1, both promoters of muscle loss.

  • acetaminophen
  • ibuprofen
  • sarcopenia
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