Accelerated sarcopenia in Cu/Zn superoxide dismutase knockout mice

Sathyaseelan S. Deepa, Holly Van Remmen, Susan V. Brooks, John A. Faulkner, Lisa Larkin, Anne McArdle, Malcolm J. Jackson, Aphrodite Vasilaki, Arlan Richardson

Research output: Contribution to journalArticle

Abstract

Mice lacking Cu/Zn-superoxide dismutase (Sod1-/- or Sod1KO mice) show high levels of oxidative stress/damage and a 30% decrease in lifespan. The Sod1KO mice also show many phenotypes of accelerated aging with the loss of muscle mass and function being one of the most prominent aging phenotypes. Using various genetic models targeting the expression of Cu/Zn-superoxide dismutase to specific tissues, we evaluated the role of motor neurons and skeletal muscle in the accelerated loss of muscle mass and function in Sod1KO mice. Our data are consistent with the sarcopenia in Sod1KO mice arising through a two-hit mechanism involving both motor neurons and skeletal muscle. Sarcopenia is initiated in motor neurons leading to a disruption of neuromuscular junctions that results in mitochondrial dysfunction and increased generation of reactive oxygen species (ROS) in skeletal muscle. The mitochondrial ROS generated in muscle feedback on the neuromuscular junctions propagating more disruption of neuromuscular junctions and more ROS production by muscle resulting in a vicious cycle that eventually leads to disaggregation of neuromuscular junctions, denervation, and loss of muscle fibers.

LanguageEnglish (US)
JournalFree Radical Biology and Medicine
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

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Sarcopenia
Knockout Mice
Neuromuscular Junction
Motor Neurons
Reactive Oxygen Species
Muscles
Skeletal Muscle
Muscle Denervation
Phenotype
Genetic Models
Oxidative Stress
Superoxide Dismutase-1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Deepa, S. S., Van Remmen, H., Brooks, S. V., Faulkner, J. A., Larkin, L., McArdle, A., ... Richardson, A. (Accepted/In press). Accelerated sarcopenia in Cu/Zn superoxide dismutase knockout mice. Free Radical Biology and Medicine. https://doi.org/10.1016/j.freeradbiomed.2018.06.032

Accelerated sarcopenia in Cu/Zn superoxide dismutase knockout mice. / Deepa, Sathyaseelan S.; Van Remmen, Holly; Brooks, Susan V.; Faulkner, John A.; Larkin, Lisa; McArdle, Anne; Jackson, Malcolm J.; Vasilaki, Aphrodite; Richardson, Arlan.

In: Free Radical Biology and Medicine, 01.01.2018.

Research output: Contribution to journalArticle

Deepa, SS, Van Remmen, H, Brooks, SV, Faulkner, JA, Larkin, L, McArdle, A, Jackson, MJ, Vasilaki, A & Richardson, A 2018, 'Accelerated sarcopenia in Cu/Zn superoxide dismutase knockout mice' Free Radical Biology and Medicine. https://doi.org/10.1016/j.freeradbiomed.2018.06.032
Deepa, Sathyaseelan S. ; Van Remmen, Holly ; Brooks, Susan V. ; Faulkner, John A. ; Larkin, Lisa ; McArdle, Anne ; Jackson, Malcolm J. ; Vasilaki, Aphrodite ; Richardson, Arlan. / Accelerated sarcopenia in Cu/Zn superoxide dismutase knockout mice. In: Free Radical Biology and Medicine. 2018.
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