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Deletion of copper-zinc superoxide dismutase (CuZnSOD) in Sodimice leads to accelerated loss of muscle mass and force during aging, but the losses do not occur with muscle-specific deletion of CuZnSOD. To determine the role of motor neurons in the muscle decline, we generated transgenic Sodl-/- mice in which CuZnSOD was expressed under control of the synapsin 1 promoter ( SynTgSodl-/- mice ) . SynTgSodl-/- mice expressed CuZnSOD in brain, spinal cord, and peripheral nerve, but not in other tissues. Sciatic nerve CuZnSOD content in SynTgSodl-/- mice was ~20% that of control mice, but no reduction in muscle mass or isometric force was observed in SynTg- Sodlmice compared with control animals, whereas muscles of age-matched Sodl-/- mice displayed 30- 40% reductions in mass and force. In addition, increased oxidative damage and adaptations in stress responses observed in muscles of Sodl-/- mice were absent in SynTgSodl-/- mice, and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sodl-/- mice but not in SynTgSodl-/- mice. Our data demonstrate that specific CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sodl-/- mice and suggest that redox homeostasis in motor neurons plays a key role in initiating sarcopenia during aging.-- Sakellariou, G. K., Davis, C. S., Shi, Y., Ivannikov, M. V., Zhang, Y., Vasilaki, A., Macleod, G. T., Richardson, A., Van Remmen, H., Jackson, M. J., McArdle, A., Brooks, S. V. Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice. [ABSTRACT FROM AUTHOR]

We have previously shown that deletion of CuZnSOD in mice (Sod1-/- mice) leads to accelerated loss of muscle mass and contractile force during aging. To dissect the relative roles of skeletal muscle and motor neurons in this process, we used a Cre-Lox targeted approach to establish a skeletal muscle-specific Sod1-knockout (mKO) mouse to determine whether muscle-specific CuZnSOD deletion is sufficient to cause muscle atrophy. Stu-prisingly, mKO mice maintain muscle masses at or above those of wild-type control mice up to 18 mo of age. In contrast, maximum isometric specific force measured in gastrocnemius muscle is significantly reduced in the mKO mice. We found no detectable increases in global measures of oxidative stress or ROS production, no reduction in mitochondrial ATP production, and no induction of adaptive stress responses in muscle from mKO mice. However, Akt-mTOR signaling is elevated and the number of muscle fibers with centrally located nuclei is increased in skeletal muscle from mKO mice, which suggests elevated regenerative pathways. Our data demoustrate that lack of CuZnSOD restricted to skeletal muscle does not lead to muscle atrophy but does cause muscle weakness in adult mice and suggest loss of CuZnSOD may potentiate muscle regenerative pathways. [ABSTRACT FROM AUTHOR]

Examines muscles of quiescent adult and old wild-type and heat shock protein 70 (HSP70) overexpressor mice for markers of oxidative damage. Ability of the muscles to activate nuclear factor-κB in response to nondamaging contractile activity; Characterization of muscle aging; Age-related changes in muscles from the HSP70 transgenic mice.

Presents a study on the effect of overexpression of heat-shock proteins70 (HSP70) in mouse skeletal muscle on muscle damage and age-related muscle dysfunction. Protection against lengthening contraction-induced damage by transgenic overexpression of HSP70 in skeletal muscle; Recovery of muscles of adult and old HSP70 transgenic mice compared to muscles of age-matched wild-type mice; Conclusion of the study.