title: Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high-intensity exercise training.
abstract: Ageing is associated with an upregulation of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) in human skeletal muscle with the increased abundance of Mfn2 being exclusive to type II muscle fibres. These changes occur despite a similar content of mitochondria, as measured by COXIV, NDUFA9 and complexes in their native states (Blue Native PAGE). Following 12 weeks of high-intensity training (HIT), older adults exhibit a robust increase in mitochondria content, while there is a decline in Mfn2 in type II fibres. We propose that the upregulation of Mfn2 and MiD49 with age may be a protective mechanism to protect against mitochondrial dysfunction, in particularly in type II skeletal muscle fibres, and that exercise may have a unique protective effect negating the need for an increased turnover of mitochondria.
  
  
  
  Mitochondrial dynamics proteins are critical for mitochondrial turnover and maintenance of mitochondrial health. High-intensity interval training (HIT) is a potent training modality shown to upregulate mitochondrial content in young adults but little is known about the effects of HIT on mitochondrial dynamics proteins in older adults. This study investigated the abundance of protein markers for mitochondrial dynamics and mitochondrial content in older adults compared to young adults. It also investigated the adaptability of mitochondria to 12 weeks of HIT in older adults. Both older and younger adults showed a higher abundance of mitochondrial respiratory chain subunits COXIV and NDUFA9 in type I compared with type II fibres, with no difference between the older adults and young groups. In whole muscle homogenates, older adults had higher mitofusin-2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) contents compared to the young group. Also, older adults had higher levels of Mfn2 in type II fibres compared with young adults. Following HIT in older adults, MiD49 and Mfn2 levels were not different in whole muscle and Mfn2 content decreased in type II fibres. Increases in citrate synthase activity (55%) and mitochondrial respiratory chain subunits COXIV (37%) and NDUFA9 (48%) and mitochondrial respiratory chain complexes (∼70-100%) were observed in homogenates and/or single fibres. These findings reveal (i) a similar amount of mitochondria in muscle from young and healthy older adults and (ii) a robust increase of mitochondrial content following 12 weeks of HIT exercise in older adults.
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Victoria, Australia.|Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Wyckelsma
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Victoria, Australia.
authors.forename: Itamar
authors.initials: I
authors.lastname: Levinger
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Victoria, Australia.
authors.forename: Michael J
authors.identifier: 0000-0001-9998-0093
authors.initials: MJ
authors.lastname: McKenna
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, 3800, Melbourne, Australia.
authors.forename: Luke E
authors.initials: LE
authors.lastname: Formosa
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, 3800, Melbourne, Australia.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Ryan
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Victoria, Australia.
authors.forename: Aaron C
authors.identifier: 0000-0003-1508-748X
authors.initials: AC
authors.lastname: Petersen
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Victoria, Australia.|Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Anderson
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
authors.forename: Robyn M
authors.identifier: 0000-0003-3697-589X
authors.initials: RM
authors.lastname: Murphy
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D000072696:High-Intensity Interval Training; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C585230:MIEF2 protein, human; D024101:Mitochondrial Proteins; D010445:Peptide Elongation Factors; D003576:Electron Transport Complex IV; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; D042967:Electron Transport Complex I; C571164:NDUFA9 protein, human
keywords: ageing; exercise adaption; mitochondria; single fibre; skeletal muscle