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Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related ox

mitoq

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#1 alc

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Posted 14 November 2016 - 05:19 PM


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Abstract

Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half
the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial
dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered
the mitochondria-targeted antioxidant mitoquinone mesylate
{[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM}
to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related
loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function.
We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated
with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum
isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force.
We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial
reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes
in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined
by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration
assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment.
Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate
administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide
any protective effect in the context of muscle aging.

 

"

 

 

http://www.fasebj.or...30/11/3771.full







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