Kynurenine, a tryptophan metabolite that increases with age, induces skeletal muscle atrophy and reactive oxygen species.

Abstract

Loss of muscle mass and power with age in the form of sarcopenia is associated with a loss of independence and a substantial decrease in quality of life due to an increase in falls and fractures. The cellular and molecular mechanisms underlying sarcopenia are not well‐understood; however, heterochronic parabiosis experiments have revealed that circulating factors are likely to play a role, and reactive oxygen species (ROS) are also known to increase in skeletal muscle with aging. This study investigated the relationship between kynurenine, a circulating tryptophan metabolite which increases with age, and markers of muscle oxidative stress. C2C12 myoblasts were treated with kynurenine in a dose‐dependent manner (0, 1, 10 μM) and ROS was measured using an Amplex red assay. Female C57BL/6 mice 6 months of age were treated with kynurenine (10 mg/kg BW) or with saline (vehicle control) for 4 weeks. Muscle mass and fiber size were measured from the quadriceps femoris ex vivo, and ROS was measured from paraffin‐embedded muscle sections using immunostaining for 4HNE. ROS was increased 2‐fold in C2C12 myoblasts treated with kynurenine at both low and high concentrations (P<.01). Quadriceps weight relative to body weight was reduced (10%) and muscle fiber size was significantly lower (P<.01) in young mice treated with kynurenine compared to controls. ROS was increased by 20% (P<.05) in young mice treated with kynurenine compared to control based on 4HNE staining. Our data reveal that the circulating tryptophan metabolite kynurenine can induce muscle wasting and increase reactive oxygen species in skeletal muscle, suggesting that pharmacological approaches to inhibit kynurenine production may provide a therapeutic strategy for the prevention of sarcopenia.Support or Funding InformationFunding for this research was provided by the National Institute on Aging (P01 AG036675).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.