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 ORCID: 0000-0003-3683-8297, Vasilaki, Aphrodite ORCID: 0000-0002-5652-0895 and Richardson, Arlan (2019) Accelerated sarcopenia in Cu/Zn superoxide dismutase knockout mice. Free Radical Biology and Medicine, 132. pp. 19-23.

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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.

Item Type:	Article
Uncontrolled Keywords:	Muscle, Skeletal, Motor Neurons, Neuromuscular Junction, Animals, Mice, Knockout, Humans, Mice, Organ Specificity, Oxidative Stress, Aging, Sarcopenia, Superoxide Dismutase-1
Depositing User:	Symplectic Admin
Date Deposited:	09 Aug 2018 11:33
Last Modified:	19 Jan 2023 01:29
DOI:	10.1016/j.freeradbiomed.2018.06.032
Open Access URL:	https://dx.doi.org/10.1007/s11357-017-9975-9
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3024792