Protective effect of myostatin gene deletion on aging-related muscle metabolic decline

• Published in: Experimental gerontology Vol. 78; pp. 23 - 31
• Main Authors: Chabi, B., Pauly, M., Carillon, J., Carnac, G., Favier, F.B., Fouret, G., Bonafos, B., Vanterpool, F., Vernus, B., Coudray, C., Feillet-Coudray, C., Bonnieu, A., Lacan, D., Koechlin-Ramonatxo, C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.06.2016; Elsevier
• Subjects: Aging - drug effects; Aging - physiology; Animals; Antioxidant; Antioxidants - administration & dosage; Antioxidants - pharmacology; Diet; GDF-8 deletion; Gene Deletion; Life Sciences; Lipid Peroxidation; Male; Mice; Mice, Knockout; Mitochondria - physiology; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiology; Myostatin - genetics; Oxidation-Reduction; Oxidative Stress; Physical Conditioning, Animal; Physical Endurance; Respiratory control ratio; Running; Running capacity; SODB; Superoxide Dismutase - administration & dosage; Superoxide Dismutase - pharmacology; Running capacity; GDF-8 deletion; SODB; Antioxidant; Respiratory control ratio
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2016.01.016

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 12weeks. 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. •Specific metabolic changes due to constitutive mstn deletion in aged skeletal muscle.•Muscle hypertrophy and redox status: beneficial side effects in aged mstn KO mice.•Skeletal muscle metabolic consequences of mstn deficiency are mitigated with aging.•Antioxidant diet prevents the decline in running performance in aged mice.