Effect of lifelong overexpression of HSP70 in skeletal muscle on age-related oxidative stress and adaptation after nondamaging contractile activity.
Skeletal muscle aging is characterized by atrophy, a deficit in specific force generation, increased susceptibility to injury, and incomplete recovery after severe injury. The ability of muscles of old mice to produce heat shock proteins (HSPs) in response to stress is severely diminished. Studies in our laboratory using HSP70 overexpressor mice demonstrated that lifelong overexpression of HSP70 in skeletal muscle provided protection against damage and facilitated successful recovery after damage in muscles of old mice. The mechanisms by which HSP70 provides this protection are unclear. Aging is associated with the accumulation of oxidation products, and it has been proposed that this may play a major role in age-related muscle dysfunction. Muscles of old wild-type (WT) mice demonstrated increased lipid peroxidation, decreased glutathione content, increased catalase and superoxide dismutase (SOD) activities, and an inability to activate nuclear factor (NF)-kappaB after contractions in comparison with adult WT mice. In contrast, levels of lipid peroxidation, glutathione content, and the activities of catalase and SOD in muscles of old HSP70 overexpressor mice were similar to adult mice and these muscles also maintained the ability to activate NF-kappaB after contractions. These data provide an explanation for the preservation of muscle function in old HSP70 overexpressor mice.
Broome
Caroline S
CS
School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, United Kingdom.
Kayani
Anna C
AC
Palomero
Jesus
J
Dillmann
Wolfgang H
WH
Mestril
Ruben
R
Jackson
Malcolm J
MJ
McArdle
Anne
A
D000199:Actins / Q000235:genetics; D000375:Aging / Q000502:physiology*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D000199:Actins; D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione