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Campbell 2018 Free Radic Biol Med
Additional label 2019-01  + , Amplex UltraRed  +
Coupling states LEAK  + , OXPHOS  +
Diseases Aging;senescence  +
Enzyme TCA cycle and matrix dehydrogenases  +
Has abstract Sarcopenia and exercise intolerance are ma
Sarcopenia and exercise intolerance are major contributors to reduced quality of life in the elderly for which there are few effective treatments. We tested whether enhancing mitochondrial function and reducing mitochondrial oxidant production with SS-31 (elamipretide) could restore redox balance and improve skeletal muscle function in aged mice. Young (5 mo) and aged (26 mo) female C57BL/6Nia mice were treated for 8-weeks with 3mg/kg/day SS-31. Mitochondrial function was assessed ''in vivo'' using <sup>31</sup>P and optical spectroscopy. SS-31 reversed age-related decline in maximum mitochondrial ATP production (ATPmax) and coupling of oxidative phosphorylation (P/O). Despite the increased ''in vivo'' mitochondrial capacity, mitochondrial protein expression was either unchanged or reduced in the treated aged mice and respiration in permeabilized gastrocnemius (GAS) fibers was not different between the aged and aged+SS-31 mice. Treatment with SS-31 also restored redox homeostasis in the aged skeletal muscle. The glutathione redox status was more reduced and thiol redox proteomics indicated a robust reversal of cysteine S-glutathionylation post-translational modifications across the skeletal muscle proteome. The gastrocnemius in the age+SS-31 mice was more fatigue resistant with significantly greater mass compared to aged controls. This contributed to a significant increase in treadmill endurance compared to both pretreatment and untreated control values. These results demonstrate that the shift of redox homeostasis due to mitochondrial oxidant production in aged muscle is a key factor in energetic defects and exercise intolerance. Treatment with SS-31 restores redox homeostasis, improves mitochondrial quality, and increases exercise tolerance without an increase in mitochondrial content. Since elamipretide is currently in clinical trials these results indicate it may have direct translational value for improving exercise tolerance and quality of life in the elderly.
erance and quality of life in the elderly.  +
Has editor [[Plangger M]]  +
Has info [https://www.ncbi.nlm.nih.gov/pubmed/30597195 PMID: 30597195]  +
Has publicationkeywords Aging  + , Fatigue  + , Mitochondria  + , Oxidative stress  + , Skeletal muscle  +
Has title Campbell MD, Duan J, Samuelson AT, Gaffrey
Campbell MD, Duan J, Samuelson AT, Gaffrey MJ, Wang L, Bammler TK, Moore RJ, White CC, Kavanagh TJ, Voss JG, Szeto HH, Rabinovitch PS, Qian WJ, Marcinek DJ (2018) Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radic Biol Med 134:268-81.
aged mice. Free Radic Biol Med 134:268-81.  +
Instrument and method O2k-Fluorometer  + , Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Exercise physiology;nutrition;life style  + , Pharmacology;toxicology  + , Respiration  +
Pathways CIV  + , N  + , NS  + , ROX  + , S  +
Preparation Permeabilized tissue  +
Respiration and regulation Redox state  +
Stress Oxidative stress;RONS  +
Tissue and cell Skeletal muscle  +
Was published by MiPNetLab US WA Seattle Marcinek DJ +
Was published in journal Free Radic Biol Med +
Was published in year 2018  +
Was written by Campbell MD + , Duan J + , Samuelson AT + , Gaffrey MJ + , Wang L + , Bammler TK + , Moore RJ + , White CC + , Kavanagh TJ + , Voss JG + , Szeto HH + , Rabinovitch PS + , Qian WJ + , Marcinek DJ +
Categories Publications
Modification date
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10:41:36, 24 May 2019  +
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