title: The age-related failure of adaptive responses to contractile activity in skeletal muscle is mimicked in young mice by deletion of Cu,Zn superoxide dismutase.
abstract: In muscle, aging is associated with a failure of adaptive responses to contractile activity, and this is hypothesized to play an important role in age-related loss of muscle mass and function. Mice lacking the Cu,Zn superoxide dismutase (Cu,ZnSOD, SOD1) show an accelerated, age-related loss of muscle mass and function. This work determined whether adult mice lacking Cu,ZnSOD (Sod1(-/-) mice) show a premature failure of adaptive responses to contractions in a similar manner to old wild-type (WT) mice. Adult Sod1(-/-) mice (6-8 months of age) had a ∼30% reduction in gastrocnemius muscle mass compared with age-matched WT mice. This lower muscle mass was associated with an activation of DNA binding by NFκB and AP-1 at rest. Measurements of the activity of reactive oxygen species (ROS) in single fibres from the muscles of Sod1(-/-) mice at rest indicated an elevation in activity compared with fibres from WT mice. Following 15 min of isometric contractions, muscle fibres from WT mice showed an increase in the intracellular ROS activities and activation of NFκB and AP-1, but no changes in either ROS activity or NFκB and AP-1 activation were seen in the muscles of Sod1(-/-) mice following contractions. This pattern of changes mimics that seen in the muscles of old WT mice, suggesting that the attenuated responses to contractile activity seen in old mice result from chronic exposure to increased oxidant activity. Data support the use of the Sod1(-/-) mouse model to evaluate potential mechanisms that contribute to the loss of muscle mass and function in the elderly.
authors.affiliation: School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Aphrodite
authors.initials: A
authors.lastname: Vasilaki
authors.forename: Jack H
authors.initials: JH
authors.lastname: van der Meulen
authors.forename: Lisa
authors.initials: L
authors.lastname: Larkin
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Harrison
authors.forename: Timothy
authors.initials: T
authors.lastname: Pearson
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.forename: Susan V
authors.initials: SV
authors.lastname: Brooks
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Jackson
authors.forename: Anne
authors.initials: A
authors.lastname: McArdle
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology; D000375:Aging / Q000235:genetics; D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics; D018482:Muscle, Skeletal / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D013482:Superoxide Dismutase