title: Identification of microRNAs linked to regulators of muscle protein synthesis and regeneration in young and old skeletal muscle.
abstract: BACKGROUND
  Over the course of ageing there is a natural and progressive loss of skeletal muscle mass. The onset and progression of age-related muscle wasting is associated with an attenuated activation of Akt-mTOR signalling and muscle protein synthesis in response to anabolic stimuli such as resistance exercise. MicroRNAs (miRNAs) are novel and important post-transcriptional regulators of numerous cellular processes. The role of miRNAs in the regulation of muscle protein synthesis following resistance exercise is poorly understood. This study investigated the changes in skeletal muscle miRNA expression following an acute bout of resistance exercise in young and old subjects with a focus on the miRNA species predicted to target Akt-mTOR signalling.
  
  
  RESULTS
  Ten young (24.2±0.9 years) and 10 old (66.6±1.1 years) males completed an acute resistance exercise bout known to maximise muscle protein synthesis, with muscle biopsies collected before and 2 hours after exercise. We screened the expression of 754 miRNAs in the muscle biopsies and found 26 miRNAs to be regulated with age, exercise or a combination of both factors. Nine of these miRNAs are highly predicted to regulate targets within the Akt-mTOR signalling pathway and 5 miRNAs have validated binding sites within the 3' UTRs of several members of the Akt-mTOR signalling pathway. The miR-99/100 family of miRNAs notably emerged as potentially important regulators of skeletal muscle mass in young and old subjects.
  
  
  CONCLUSIONS
  This study has identified several miRNAs that were regulated with age or with a single bout of resistance exercise. Some of these miRNAs were predicted to influence Akt-mTOR signalling, and therefore potentially skeletal muscle mass. These miRNAs should be considered as candidate targets for in vivo modulation.
authors.affiliation: Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Zacharewicz
authors.affiliation: Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Della Gatta
authors.affiliation: Biostatistics Unit, Faculty of Health, Deakin University, Burwood, Victoria, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Reynolds
authors.affiliation: Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Garnham
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia; Australian Animal Health Laboratory, CSIRO Animal, Food and Health Sciences, Waurn Ponds, Victoria, Australia.
authors.forename: Tamsyn
authors.initials: T
authors.lastname: Crowley
authors.affiliation: Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
authors.affiliation: Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia.
authors.forename: Séverine
authors.initials: S
authors.lastname: Lamon
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D019295:Computational Biology; D016002:Discriminant Analysis; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D025341:Principal Component Analysis; D012038:Regeneration / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs