Regulation of antioxidant defenses in the prevention of skeletal muscle deconditioning
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Regulation of antioxidant defenses in the prevention of skeletal muscle deconditioning

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Regulation of antioxidant defenses in the prevention of skeletal muscle deconditioning

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dc.contributor.advisor Viña Ribes, José
dc.contributor.advisor Gómez Cabrera, María Carmen
dc.contributor.advisor Chopard, Angèle
dc.contributor.advisor Brioche, Thomas
dc.contributor.author Arc-Chagnaud, Coralie
dc.contributor.other Departament de Fisiologia es_ES
dc.date.accessioned 2019-10-30T08:04:27Z
dc.date.available 2019-10-31T05:45:05Z
dc.date.issued 2019 es_ES
dc.date.submitted 22-11-2019 es_ES
dc.identifier.uri https://hdl.handle.net/10550/71832
dc.description.abstract Musculoskeletal system plays a key role in organism’s well functioning and is responsible for a large variety of functions such as posture, locomotion, balance, and activities of daily life. The quality of the skeletal muscle is therefore capital to maintain quality of life and, in the long term, survival. Hypoactivity and aging are two situations that cause skeletal muscle deconditioning, therefore sharing common characteristics: loss of muscle strength, muscular atrophy and MyHC redistribution, as well as IMAT accumulation. To date, there is plenty of evidence supporting a causative link between oxidative stress phenomenon and muscle deconditioning. The two studies exposed in this thesis demonstrated that modulate antioxidant defense systems have important consequences on deconditioned skeletal muscle tissue. The first study aimed to evaluate frailty in old female animals, using WT and G6PD overexpressing mice. We did a longitudinal functional evaluation, testing the mice each 2 months from 18 to 26 months of age, and then we calculated a frailty score in both groups. In muscle samples of 21-month old mice, we evaluated muscle quality parameters and oxidative stress markers. Finally, we performed a transcriptomic analysis of muscle samples and highlighted differentially expressed genes in both groups of mice. The second study was conducted to evaluate the effects of a cocktail enriched in antioxidant/anti-inflammatory molecules in a 2-month hypoactivity experiment. This countermeasure was expected to limit the effects of muscle deconditioning, but our results clearly demonstrate the ineffectiveness of this type of supplementation in the prevention of muscle mass and strength loss. Moreover, data regarding muscle molecular mechanisms highlight an alteration of recovery processes in the supplemented subjects. These results can be explained by an inhibition of the beneficial adaptations induced by the presence of RONS and illustrate the necessity of pro-oxidant molecules during long-term inactivity to maintain a certain level of muscle function. It underlines the complexity of redox balance mechanisms and demonstrates that physiological amounts of RONS are essential to activate molecular pathways and preserve positive adaptations. Finally, the conclusions of our two studies gave clues on the suitable antioxidant modulation strategy for the prevention of skeletal muscle deconditioning. It seems preferable to focus on the stimulation of endogenous defense system whether than towards exogenous supply of nutritional antioxidants. Nevertheless, the complexity of redox signaling requires better understanding to optimize countermeasures in muscle wasting situations. es_ES
dc.format.extent 306 p. es_ES
dc.language.iso en es_ES
dc.subject oxidative stress es_ES
dc.subject skeletal muscle deconditioning es_ES
dc.subject antioxidant defenses es_ES
dc.subject aging es_ES
dc.subject hypoactivity es_ES
dc.title Regulation of antioxidant defenses in the prevention of skeletal muscle deconditioning es_ES
dc.type info:eu-repo/semantics/doctoralThesis es_ES
dc.subject.unesco UNESCO::CIENCIAS MÉDICAS es_ES
dc.subject.unesco UNESCO::CIENCIAS DE LA VIDA es_ES
dc.description.abstractenglish Musculoskeletal system plays a key role in organism’s well functioning and is responsible for a large variety of functions such as posture, locomotion, balance, and activities of daily life. The quality of the skeletal muscle is therefore capital to maintain quality of life and, in the long term, survival. Hypoactivity and aging are two situations that cause skeletal muscle deconditioning, therefore sharing common characteristics: loss of muscle strength, muscular atrophy and MyHC redistribution, as well as IMAT accumulation. To date, there is plenty of evidence supporting a causative link between oxidative stress phenomenon and muscle deconditioning. The two studies exposed in this thesis demonstrated that modulate antioxidant defense systems have important consequences on deconditioned skeletal muscle tissue. The first study aimed to evaluate frailty in old female animals, using WT and G6PD overexpressing mice. We did a longitudinal functional evaluation, testing the mice each 2 months from 18 to 26 months of age, and then we calculated a frailty score in both groups. In muscle samples of 21-month old mice, we evaluated muscle quality parameters and oxidative stress markers. Finally, we performed a transcriptomic analysis of muscle samples and highlighted differentially expressed genes in both groups of mice. The second study was conducted to evaluate the effects of a cocktail enriched in antioxidant/anti-inflammatory molecules in a 2-month hypoactivity experiment. This countermeasure was expected to limit the effects of muscle deconditioning, but our results clearly demonstrate the ineffectiveness of this type of supplementation in the prevention of muscle mass and strength loss. Moreover, data regarding muscle molecular mechanisms highlight an alteration of recovery processes in the supplemented subjects. These results can be explained by an inhibition of the beneficial adaptations induced by the presence of RONS and illustrate the necessity of pro-oxidant molecules during long-term inactivity to maintain a certain level of muscle function. It underlines the complexity of redox balance mechanisms and demonstrates that physiological amounts of RONS are essential to activate molecular pathways and preserve positive adaptations. Finally, the conclusions of our two studies gave clues on the suitable antioxidant modulation strategy for the prevention of skeletal muscle deconditioning. It seems preferable to focus on the stimulation of endogenous defense system whether than towards exogenous supply of nutritional antioxidants. Nevertheless, the complexity of redox signaling requires better understanding to optimize countermeasures in muscle wasting situations es_ES
dc.embargo.terms 0 days es_ES

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