Overexpression of HSP70 in mouse skeletal muscle protects against muscle damage and age-related muscle dysfunction.
Ageing is associated with skeletal muscle atrophy, a deficit in force generation, an increased susceptibility to contraction-induced injury, and a permanent force deficit following severe injury. Muscles of young mice adapt rapidly following exercise by an increase in the production of heat shock proteins (HSPs), whereas muscles of old mice show a severely diminished response. We hypothesized that overexpression of HSP70 in muscle throughout life would reduce age-related changes in function. The maximum tetanic force of extensor digitorum longus (EDL) muscles of adult and old wild-type (WT) and HSP70 overexpressor transgenic mice was determined. EDL muscles were subjected to damaging lengthening contractions and the ability to generate force was assessed for up to 28 days following the contractions. Overexpression of HSP70 in muscles of old transgenic mice prevented the specific force deficit observed in muscles of old WT mice. The complete recovery of muscles of old HSP70 transgenic mice by 14 days following the contraction protocol was in contrast to the 44% force deficit, which remained in muscles of old WT mice at 28 days following the protocol. These data indicate that a diminished production of HSP70 in muscles of old mammals has a major effect on age-related functional deficits.
McArdle
Anne
A
Department of Medicine, University of Liverpool, Liverpool L69 3GA, UK. mdcr02@liv.ac.uk
Dillmann
Wolfgang H
WH
Mestril
Ruben
R
Faulkner
John A
JA
Jackson
Malcolm J
MJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D009135:Muscular Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D019076:Transgenes / Q000235:genetics
D018840:HSP70 Heat-Shock Proteins