title: Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice.
abstract: There is much interest in the capacity of resistance exercise to prevent the age-related loss of skeletal muscle mass and function, known as sarcopenia. This study investigates the molecular basis underlying the benefits of resistance exercise in aging C57BL/6J mice of both sexes.
  
  
  
  This study is the first to demonstrate that long-term (34 weeks) voluntary resistance wheel exercise (RWE) initiated at middle age, from 15 months, prevents sarcopenia in selected hindlimb muscles and causes hypertrophy in soleus, by 23 months of age in both male and female C57BL/6J mice. Compared with 23-month-old sedentary (SED) controls, RWE (0-6 g of resistance) increased intramuscular mitochondrial density and oxidative capacity (measured by citrate synthase and NADH-TR) and increased LC3II/I ratios (a marker of autophagy) in exercised mice of both sexes. RWE also reduced mRNA expression of Gadd45α (males only) and Runx1 (females only) but had no effect on other markers of denervation including Chrng, Chrnd, Musk, and Myog. RWE increased heart mass in all mice, with a more pronounced increase in females. Significant sex differences were also noted among SED mice, with Murf1 mRNA levels increasing in male, but decreasing in old female mice between 15 and 23 months.
  
  
  
  Overall, long-term RWE initiated from 15 month of age significantly improved some markers of the mitochondrial and autophagosomal pathways and prevented age-related muscle wasting.
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia (UWA), 35 Stirling Highway, Crawley, WA, 6009, Australia.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, UWA and Harry Perkins Institute of Medical Research, Crawley, 6009, WA, Australia.
authors.forename: Zoe
authors.initials: Z
authors.lastname: White
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia (UWA), 35 Stirling Highway, Crawley, WA, 6009, Australia.|School of Chemistry and Biochemistry, UWA, Crawley, 6009, WA, Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Terrill
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia (UWA), 35 Stirling Highway, Crawley, WA, 6009, Australia.
authors.forename: Robert B
authors.initials: RB
authors.lastname: White
authors.affiliation: Developmental Biology Group, AgResearch Ltd, Hamilton, 3214, New Zealand.
authors.forename: Christopher
authors.initials: C
authors.lastname: McMahon
authors.affiliation: Department of Physiology, University of Otago, Dunedin, 9010, New Zealand.
authors.forename: Phillip
authors.initials: P
authors.lastname: Sheard
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia (UWA), 35 Stirling Highway, Crawley, WA, 6009, Australia. miranda.grounds@uwa.edu.au.
authors.forename: Miranda D
authors.initials: MD
authors.lastname: Grounds
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia (UWA), 35 Stirling Highway, Crawley, WA, 6009, Australia.
authors.forename: Tea
authors.initials: T
authors.lastname: Shavlakadze
mesh_terms: D000818:Animals; D001343:Autophagy; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D055948:Sarcopenia / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D012737:Sex Factors; D000070584:Tripartite Motif Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D009124:Muscle Proteins; D018008:Myogenin; D009687:Nuclear Proteins; D020794:Receptor Protein-Tyrosine Kinases; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; C552917:Chrnd protein, mouse; C499072:Gadd45a protein, mouse; D000097642:GADD45 Proteins; C503801:Myog protein, mouse; C493726:Runx1 protein, mouse; C559497:acetylcholine receptor gamma, mouse; C499084:Trim63 protein, mouse; C511695:MuSK protein, mouse
keywords: Aging; Autophagy; Citrate synthase; Denervation; Mitochondria; Muscle; Oxidative capacity; Resistance exercise; Sarcopenia