title: Overexpression of HSP10 in skeletal muscle of transgenic mice prevents the age-related fall in maximum tetanic force generation and muscle Cross-Sectional Area.
abstract: Skeletal muscle atrophy and weakness are major contributors to frailty and impact significantly on quality of life of older people. Muscle aging is characterized by a loss of maximum tetanic force (P(o)) generation, primarily due to muscle atrophy, to which mitochondrial dysfunction is hypothesized to contribute. We hypothesized that lifelong overexpression of the mitochondrial heat shock protein (HSP) HSP10 in muscle of mice would protect against development of these deficits. P(o) generation by extensor digitorum longus muscles of adult and old wild-type and HSP10-overexpressing mice was determined in situ. Muscles were subjected to damaging lengthening contractions, and force generation was remeasured at 3 h or 28 days to examine susceptibility to, and recovery from, damage, respectively. Muscles of old wild-type mice had a 23% deficit in P(o) generation and a 10% deficit in muscle cross-sectional area compared with muscles of adult wild-type mice. Overexpression of HSP10 prevented this age-related fall in P(o) generation and reduction in cross-sectional area observed in muscles of old wild-type mice. Additionally, overexpression of HSP10 protected against contraction-induced damage independent of age but did not improve recovery if damage occurred. Preservation of muscle force generation and CSA by HSP10 overexpression was associated with protection against the age-related accumulation of protein carbonyls. Data demonstrate that development of age-related muscle weakness may not be inevitable and show, for the first time, that lifelong overexpression of an HSP prevents the age-related loss of P(o) generation. These findings support the hypothesis that mitochondrial dysfunction is involved in the development of age-related muscle deficits.
authors.affiliation: Pathophysiology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Kayani
authors.forename: Graeme L
authors.initials: GL
authors.lastname: Close
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Dillmann
authors.forename: Ruben
authors.initials: R
authors.lastname: Mestril
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Jackson
authors.forename: Anne
authors.initials: A
authors.lastname: McArdle
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism*; D019563:Mechanics; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000502:physiology; D018908:Muscle Weakness / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013746:Tetany / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D006360:Heat-Shock Proteins
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