title: Roles of sedentary aging and lifelong physical activity in exchange of glutathione across exercising human skeletal muscle.
abstract: Reactive oxygen species (ROS) are important signaling molecules with regulatory functions, and in young and adult organisms, the formation of ROS is increased during skeletal muscle contractions. However, ROS can be deleterious to cells when not sufficiently counterbalanced by the antioxidant system. Aging is associated with accumulation of oxidative damage to lipids, DNA, and proteins. Given the pro-oxidant effect of skeletal muscle contractions, this effect of age could be a result of excessive ROS formation. We evaluated the effect of acute exercise on changes in blood redox state across the leg of young (23 ± 1 years) and older (66 ± 2 years) sedentary humans by measuring the whole blood concentration of the reduced (GSH) and oxidized (GSSG) forms of the antioxidant glutathione. To assess the role of physical activity, lifelong physically active older subjects (62 ± 2 years) were included. Exercise increased the venous concentration of GSSG in an intensity-dependent manner in young sedentary subjects, suggesting an exercise-induced increase in ROS formation. In contrast, venous GSSG levels remained unaltered during exercise in the older sedentary and active groups despite a higher skeletal muscle expression of the superoxide-generating enzyme NADPH oxidase. Arterial concentration of GSH and expression of antioxidant enzymes in skeletal muscle of older active subjects were increased. The potential impairment in exercise-induced ROS formation may be an important mechanism underlying skeletal muscle and vascular dysfunction with sedentary aging. Lifelong physical activity upregulates antioxidant systems, which may be one of the mechanisms underlying the lack of exercise-induced increase in GSSG.
authors.affiliation: Department of Nutrition, Exercise, and Sports, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark; Copenhagen Muscle Research Centre and University of Southern Denmark, Copenhagen, Denmark. Electronic address: mnyberg@ifi.ku.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Nyberg
authors.affiliation: Copenhagen Muscle Research Centre and University of Southern Denmark, Copenhagen, Denmark; Department of Cardiovascular and Renal Research, University of Southern Denmark, Copenhagen, Denmark.
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Mortensen
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, and Fundación Investigacion Hospital Clinico Universitario/INCLIVA, Valencia, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Cabo
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, and Fundación Investigacion Hospital Clinico Universitario/INCLIVA, Valencia, Spain.
authors.forename: Mari-Carmen
authors.initials: MC
authors.lastname: Gomez-Cabrera
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, and Fundación Investigacion Hospital Clinico Universitario/INCLIVA, Valencia, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Viña
authors.affiliation: Department of Nutrition, Exercise, and Sports, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark; Copenhagen Muscle Research Centre and University of Southern Denmark, Copenhagen, Denmark.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hellsten
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D000975:Antioxidants / Q000032:analysis; D002374:Catalase / Q000096:biosynthesis; D015444:Exercise / Q000502:physiology*; D005978:Glutathione / Q000097:blood*; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D006801:Humans; D007866:Leg / Q000502:physiology; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D019255:NADPH Oxidases / Q000096:biosynthesis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D057185:Sedentary Behavior; D013482:Superoxide Dismutase / Q000096:biosynthesis; D000072105:Superoxide Dismutase-1; D055815:Young Adult; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D002374:Catalase; D005978:Glutathione; D005979:Glutathione Peroxidase; D019255:NADPH Oxidases; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human; C079789:neutrophil cytosol factor 67K; C000722067:GPX1 protein, human
keywords: Agingra; Antioxidants; Free radicals; Glutathione; Reactive oxygen species; Skeletal muscle