title: Protective effect of myostatin gene deletion on aging-related muscle metabolic decline.
abstract: While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; p<0.05) in skeletal muscle from aged KO mice; however, differences with WT mice were attenuated at old age in line with reduced difference on running endurance between the two genotypes. Interestingly, we showed an increase in glutathione levels, associated with lower lipid peroxidation levels in KO muscle. Enriched antioxidant diet reduced the aging-related negative effects on maximal aerobic velocity and running limit time (p<0.05) in both groups, with systemic adaptations on body weight. The redox status and the hypertrophic phenotype appeared to be beneficial to KO mice, mitigating the effect of aging on the skeletal muscle metabolic remodeling.
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: B
authors.initials: B
authors.lastname: Chabi
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Pauly
authors.affiliation: Bionov Sarl, Avignon, France.
authors.forename: J
authors.initials: J
authors.lastname: Carillon
authors.affiliation: Inserm U1046, Université ́ Montpellier, 34295 Montpellier, France.
authors.forename: G
authors.initials: G
authors.lastname: Carnac
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: F B
authors.initials: FB
authors.lastname: Favier
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: G
authors.initials: G
authors.lastname: Fouret
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: B
authors.initials: B
authors.lastname: Bonafos
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Vanterpool
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: B
authors.initials: B
authors.lastname: Vernus
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Coudray
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Feillet-Coudray
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Bonnieu
authors.affiliation: Bionov Sarl, Avignon, France.
authors.forename: D
authors.initials: D
authors.lastname: Lacan
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier, F-34060, Montpellier, France. Electronic address: christelle.ramonatxo@umontpellier.fr.
authors.forename: C
authors.initials: C
authors.lastname: Koechlin-Ramonatxo
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D004032:Diet; D017353:Gene Deletion; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D055435:Myostatin / Q000235:genetics*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D012420:Running; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000975:Antioxidants; C525912:Mstn protein, mouse; D055435:Myostatin; D013482:Superoxide Dismutase
keywords: Antioxidant; GDF-8 deletion; Respiratory control ratio; Running capacity; SODB