title: Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy.
abstract: We describe a novel phenotype in mice lacking the major antioxidant enzyme, CuZn-superoxide dismutase (Sod1(-/-) mice), namely a dramatic acceleration of age-related loss of skeletal muscle mass. Sod1(-/-) mice are 17 to 20% smaller and have a significantly lower muscle mass than wild-type mice as early as 3 to 4 months of age. Muscle mass in the Sod1(-/-) mice is further reduced with age and by 20 months, the hind-limb muscle mass in Sod1(-/-) mice is nearly 50% lower than in age-matched wild-type mice. Skeletal muscle tissue from young Sod1(-/-) mice has elevated oxidative damage to proteins, lipids, and DNA compared to muscle from young wild-type mice. The reduction in muscle mass and elevated oxidative damage are accompanied by a 40% decrease in voluntary wheel running by 6 months of age and decreased performance on the Rota-rod test at 13 months of age, but are not associated with a decline in overall spontaneous activity. In some of the old Sod1(-/-) mice, the loss in muscle mass is also associated with the presence of tremors and gait disturbances. Thus, the absence of CuZnSOD imposes elevated oxidative stress, loss of muscle mass, and physiological consequences that resemble an acceleration of normal age-related sarcopenia.
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
authors.forename: Florian L
authors.initials: FL
authors.lastname: Muller
authors.forename: Wook
authors.initials: W
authors.lastname: Song
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Asish
authors.initials: A
authors.lastname: Chaudhuri
authors.forename: Sandra
authors.initials: S
authors.lastname: Pieke-Dahl
authors.forename: Randy
authors.initials: R
authors.lastname: Strong
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Huang
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Epstein
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Marie
authors.initials: M
authors.lastname: Csete
authors.forename: John A
authors.initials: JA
authors.lastname: Faulkner
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
mesh_terms: D000375:Aging / Q000473:pathology*; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000473:pathology*; D009133:Muscular Atrophy; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase