Influence of low‐dose aspirin, resistance exercise, and sex on human skeletal muscle PGE₂/COX pathway activity

Abstract

Prostaglandin (PG) E2 has been linked to increased inflammation and attenuated resistance exercise adaptations in skeletal muscle. Nonaspirin cyclooxygenase (COX) inhibitors have been shown to reduce these effects. This study examined the effect of low‐dose aspirin on skeletal muscle COX production of PGE2 at rest and following resistance exercise. Skeletal muscle (vastus lateralis) biopsies were taken from six individuals (4 M/2 W) before and 3.5 hr after a single bout of resistance exercise for ex vivo PGE2 production under control and low (10 μM)‐ or standard (100 μM)‐dose aspirin conditions. Sex‐specific effects of aspirin were also examined by combining the current findings with our previous similar ex vivo skeletal muscle investigations (n = 20, 10 M/10 W). Low‐dose aspirin inhibited skeletal muscle PGE2 production (p < 0.05). This inhibition was similar to standard‐dose aspirin (p > 0.05) and was not influenced by resistance exercise (p > 0.05) (overall effect: −18 ± 5%). Men and women had similar uninhibited skeletal muscle PGE2 production at rest (men: 1.97 ± 0.33, women: 1.96 ± 0.29 pg/mg wet weight/min; p > 0.05). However, skeletal muscle of men was 60% more sensitive to aspirin inhibition than women (p < 0.05). In summary, the current findings 1) confirm low‐dose aspirin inhibits the PGE2/COX pathway in human skeletal muscle, 2) show that resistance exercise does not alter aspirin inhibitory efficacy, and 3) suggest the skeletal muscle of men and women could respond differently to long‐term consumption of low‐dose aspirin, one of the most common chronically consumed drugs in the world.

Controlling Inflammation Improves Aging Skeletal Muscle Health

“…Yet, the COX pathway has emerged as a potential regulator of the health and function of aging skeletal muscle. It is noteworthy that this pathway seems to be involved in the inflammatory-regulated health of several other tissues, which provides indirect support for the proposed hypothesis in skeletal muscle (78)(79)(80)(81)(82)(83)(84). Preclinical investigations combined with observations from prospective randomized controlled trials may provide further insight into the complex nature of regulating age-associated COX inhibition in skeletal muscle tissue.…”

Influence of aspirin on aging skeletal muscle: Insights from a cross‐sectional cohort of septuagenarians

“…This investigation, through the large and diverse cohort provided by Health ABC, offers the first large‐scale insight into the potential influence of chronic COX inhibition via aspirin on direct measurements of skeletal muscle size in older individuals. The lack of influence of aspirin on skeletal muscle size of two important upper leg muscle groups between non‐consumers and aspirin consumers was interesting considering the known effect of aspirin on the COX pathway in human skeletal muscle (Fountain et al, 2020 ; Naruse et al, 2021 ; Ratchford et al, 2017 ). In agreement with these muscle size findings was the lack of aspirin influence on muscle strength and circulating IL‐6.…”

“…The most common mechanism of action of drugs in this class is inhibition of the COX pathway and several of these drugs have been shown to reduce human skeletal muscle COX pathway activity (Boushel et al, 2002 ; Burian et al, 2013 ; Fountain et al, 2020 ; Naruse et al, 2021 ; Ratchford et al, 2017 ; Trappe et al, 2001 ). Aspirin (IDIS: 28080751) was the most prevalent COX‐inhibitor in Health ABC, followed by acetaminophen (IDIS: 28081221), ibuprofen (IDIS: 28080509), naproxen (IDIS: 28080513), nabumetone (IDIS: 28080459), etodolac (IDIS: 28080455), diclofenac (IDIS: 28080422), sulindac (IDIS: 28080428), indomethacin (IDIS: 28080463), ketoprofen (IDIS: 28080512), oxaprozin (IDIS: 28080466), meclofenamate sodium (IDIS: 28080412), tolmetin (IDIS: 28080420), piroxicam (IDIS: 28080437), fenoprofen (IDIS: 28080506), flurbiprofen (IDIS: 28080507), celecoxib (IDIS: 28080601), choline salicylate (IDIS: 28080752), magnesium salicylate (IDIS: 28080756), phenyl salicylate (IDIS: 28080761), salsalate (IDIS: 28080764), diflusinal (IDIS: 28080768), and ketorolac (IDIS: 28081219).…”

“…The cyclooxygenase (COX) pathway is an established component of inflammation‐associated regulatory mechanisms in various tissues including skeletal muscle (Korotkova & Lundberg, 2014 ; Trappe & Liu, 2013 ). Aspirin has been shown to be a potent COX inhibitor in human skeletal muscle, even at low doses (Fountain et al, 2020 ; Naruse et al, 2021 ; Ratchford et al, 2017 ). Inhibition of the COX pathway in skeletal muscle alters prostaglandin production, muscle protein turnover, inflammation associated pathways, and ultimately has been shown to influence skeletal muscle mass (Trappe et al, 2016 ; Trappe & Liu, 2013 ).…”

Hepatic Steatosis Contributes to the Development of Muscle Atrophy via Inter-Organ Crosstalk

“…‘Prostaglandin Synthesis and Regulation’ and ‘Arachidonic acid metabolism’ are also relevant pathways that were enriched. Prostaglandins are mainly synthesized from arachidonic acid and are known to be major regulators of skeletal muscle protein turnover and exercise training adaptations ( 38 , 39 ). Altogether, our results suggest that HFD CM leads toward a dysregulation of a set of genes with important roles in the maintenance of muscle mass and health.…”