title: The functional consequences of age-related changes in microRNA expression in skeletal muscle.
abstract: A common characteristic of ageing is disrupted homeostasis between growth and atrophy of skeletal muscle resulting in loss of muscle mass and function, which is associated with sarcopenia. Sarcopenia is related to impaired balance, increased falls and decline in quality of life of older people. Ageing-related transcriptome and proteome changes in skeletal muscle have been characterised, however the molecular mechanisms underlying sarcopenia are still not fully understood. microRNAs are novel regulators of gene expression known to modulate skeletal muscle development and homeostasis. Expression of numerous microRNAs is disrupted in skeletal muscle with age however, the functional consequences of this are not yet understood. Given that a single microRNA can simultaneously affect multiple signalling pathways, microRNAs are potent modulators of pathophysiological changes occurring during ageing. Here we use microRNA and transcript expression profiling together with microRNA functional assays to show that disrupted microRNA:target interactions play an important role in maintaining muscle homeostasis. We identified miR-181a as a regulator of the sirtuin1 (Sirt1) gene expression in skeletal muscle and show that the expression of miR-181a and its target gene is disrupted in skeletal muscle from old mice. Moreover, we show that miR-181a:Sirt1 interactions regulate myotube size. Our results demonstrate that disrupted microRNA:target interactions are likely related to the pathophysiological changes occurring in skeletal muscle during ageing.
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Apex Building, West Derby Road, Liverpool, L8 7TX, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Soriano-Arroquia
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Apex Building, West Derby Road, Liverpool, L8 7TX, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: House
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Apex Building, West Derby Road, Liverpool, L8 7TX, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Tregilgas
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Apex Building, West Derby Road, Liverpool, L8 7TX, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Canty-Laird
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Apex Building, West Derby Road, Liverpool, L8 7TX, UK. k.whysall@liverpool.ac.uk.
authors.forename: Katarzyna
authors.identifier: 0000-0001-8166-8800
authors.initials: K
authors.lastname: Goljanek-Whysall
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D055948:Sarcopenia / Q000378:metabolism* / Q000473:pathology*
chemical_list: D035683:MicroRNAs
keywords: Ageing; Muscle; Sarcopenia; Sirt1; microRNA