Campbell 2015 Abstract IOC100

From Bioblast
Campbell MD (2015) Improved redox state increases aged skeletal muscle performance. Mitochondr Physiol Network 20.01.

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Campbell MD (2015)

Event: IOC100

The decline in skeletal muscle performance with age (sarcopenia) is a significant public health concern due to the effect on quality of life and loss of independence. Mitochondrial oxidative stress has been thought to be a key mediator of age-related degeneration in skeletal muscle, although recent reports have challenged this view. Previously our lab has demonstrated that directly targeting mitochondrial oxidative stress and energetics using a single acute treatment with the mitochondrial-targeted peptide SS-31 reduces oxidative stress and improves muscle function in aged mice. However, whether long-term treatment with SS-31 peptide prevents sarcopenia and improves exercise tolerance is still unknown. We used osmotically controlled pumps to deliver a dose of SS-31 peptide equivalent to 3 mg/kg of body mass per day for 4 or 8 weeks to 7 and 26-month old mice. After 4 and 8 weeks SS-31 treatment led to an increase in both running distance and time in 26-month old mice using a ramped treadmill protocol compared to saline treated controls. The increase in exercise tolerance also correlated with an improvement of in-situ fatigue resistance among aged mice treated with SS-31 peptide for 8 weeks. To test whether changes in redox signaling could underlie mitochondrial and muscle deficits with age we used a thiol redox proteomics approach. Aging results in a significant increase in protein S-glutathionylation (PSSG) that was partially reversed with SS-31 treatment. Cysteine residues sensitive to PSSG with age and reversal by SS-31 treatment exist in many different cellular systems including but not limited to cellular contractility, glycolysis, oxidative phosphorylation, membrane repair, and control of redox signaling. Our preliminary data supports the conclusion that SS-31 represents a novel intervention with excellent translational potential to improve skeletal muscle function in the elderly.


Labels: MiParea: Exercise physiology;nutrition;life style, Patients  Pathology: Aging;senescence  Stress:Oxidative stress;RONS  Organism: Mouse 






Affiliations

Marcinek Lab, Dept Radiology, Univ Washington, Seattle; USA. - mdcampbe@uw.edu

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