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Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle
Nye, Gareth Sakellariou, Giorgos Lightfoot, Adam Pearson, Timothy Wells, Nicola McArdle, Anne Jackson, Malcolm Giakoumaki, Ifigeneia Griffiths, Richard
Nye, Gareth
Sakellariou, Giorgos
Lightfoot, Adam
Pearson, Timothy
Wells, Nicola
McArdle, Anne
Jackson, Malcolm
Giakoumaki, Ifigeneia
Griffiths, Richard
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EPub Date
Publication Date
2016-08-22
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fj.201600450r.pdf
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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
Citation
Sakellariou, G., Pearson, T., Lightfoot, A., Nye, G., Wells, N., Giakoumaki, I., . . . Jackson, M. (2016). Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle. Faseb Journal, 30(11), 3771-3785.
Publisher
Faseb Journal
Journal
Faseb Journal
Research Unit
DOI
10.1096/fj.201600450R
PubMed ID
PubMed Central ID
Type
Article
Language
en
Description
Series/Report no.
ISSN
0892-6638
EISSN
1530-6860