Musculoskeletal ageing in transgenic mice overexpressing HSP70.





A McArdle1, A Vasilaki1, W Dillmann2, R Mestril3, JA Faulkner4, MJ Jackson1.

1University of Liverpool, UK, 2University of California, San Diego, 3Loyola University Chicago and 4University of Michigan.




As we age, our skeletal muscles become smaller and weaker. They are more susceptible to damage and take longer to recover from damage (1,2,3). The mechanism behind this age-related deficit is unknown. However, recent data from our laboratory suggests that part of this age-related functional deficit may be due to a failure of skeletal muscle from aged mammals to adapt following stress. Skeletal muscle contains a highly conserved family of proteins known as stress or heat shock proteins (HSPs; 4,5). In the unstressed cell, these proteins act as molecular chaperones, facilitating the correct folding of newly synthesised proteins. Skeletal muscle responds to stress, particularly exercise-induced stress, by the increased production of HSPs (4) and this adaptive response is thought to be necessary for subsequent remodelling of tissue and to provide cytoprotection against subsequent damaging stresses.

In recent studies, we have demonstrated that the ability of skeletal muscle from aged rodents to produce HSPs following exercise is severely blunted (6). Recent data from our laboratory using transgenic mice, has shown that maintenance of the muscle HSP70 content throughout life provides some protection against the development of age-related deficits in skeletal muscle, particularly, the specific force of muscle and ability to regenerate following damage. This data has demonstrated that a comprehensive understanding of the age-related failure of the stress response would have significant impact on the maintenance of strength in muscles of older people.

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The authors would like to thank Research into Ageing and The Wellcome Trust for funding this work.







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