Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy

Florian L. Muller, Wook Song, Yuhong Liu, Asish Chaudhuri, Sandra Pieke-Dahl, John R Strong, Ting Ting Huang, Charles J. Epstein, L. Jackson Roberts, Marie Csete, John A. Faulkner, Holly Van Remmen

Research output: Contribution to journalArticle

255 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1993-2004
Number of pages12
JournalFree Radical Biology and Medicine
Volume40
Issue number11
DOIs
StatePublished - Jun 1 2006

Fingerprint

Oxidative stress
Muscular Atrophy
Superoxide Dismutase
Muscle
Skeletal Muscle
Oxidative Stress
Muscles
Sarcopenia
Tremor
Gait
Running
Wheels
Antioxidants
Extremities
Tissue
Lipids
Phenotype
DNA

Keywords

  • Aging
  • CuZnSOD
  • Free radicals
  • Muscle atrophy
  • Oxidative stress
  • Superoxide

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy. / Muller, Florian L.; Song, Wook; Liu, Yuhong; Chaudhuri, Asish; Pieke-Dahl, Sandra; Strong, John R; Huang, Ting Ting; Epstein, Charles J.; Roberts, L. Jackson; Csete, Marie; Faulkner, John A.; Van Remmen, Holly.

In: Free Radical Biology and Medicine, Vol. 40, No. 11, 01.06.2006, p. 1993-2004.

Research output: Contribution to journalArticle

Muller, FL, Song, W, Liu, Y, Chaudhuri, A, Pieke-Dahl, S, Strong, JR, Huang, TT, Epstein, CJ, Roberts, LJ, Csete, M, Faulkner, JA & Van Remmen, H 2006, 'Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy', Free Radical Biology and Medicine, vol. 40, no. 11, pp. 1993-2004. https://doi.org/10.1016/j.freeradbiomed.2006.01.036
Muller, Florian L. ; Song, Wook ; Liu, Yuhong ; Chaudhuri, Asish ; Pieke-Dahl, Sandra ; Strong, John R ; Huang, Ting Ting ; Epstein, Charles J. ; Roberts, L. Jackson ; Csete, Marie ; Faulkner, John A. ; Van Remmen, Holly. / Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy. In: Free Radical Biology and Medicine. 2006 ; Vol. 40, No. 11. pp. 1993-2004.
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