Skeletal muscle of young rodents responds to a demanding contraction protocol by an increased production of stress or heat shock proteins (HSPs; McArdle et al. 2001). Skeletal muscles of ageing rodents are characterised by a severe attenuation of this ability to produce HSPs in response to a demanding contraction protocol (Vasilaki et al. 2002). The functional effect of this attenuated response is not known. This study has used transgenic mice to examine the role that this attenuated stress response plays in the susceptibility of muscles to contraction-induced injury and the nature of recovery following this injury.

Mice were anaesthetised by I.P. injection of sodium pentobarbitone (65 mg (100 g body wt)^-1). Extensor digitorum longus muscles of adult (12Ð14 months) and old (26Ð30 months) wild-type and transgenic mice, over-expressing HSP70 (Marber et al. 1995), were subjected to damaging lengthening contractions (3 X 5 min periods of contractions, with 5 min intervals, during which the muscle was activated at 150 Hz and lengthened by 20 % of fibre length every 2 s). At 3 h, and 3, 14 and 28 days following the contraction protocol, mice were anaesthetised and the recovery of muscles was measured by the ability to generate maximum force. Mice were humanely killed by overdose of sodium pentobarbitone. Muscle structure, biochemical and immunohistochemical markers of muscle damage and regeneration were assessed. Data are presented as means ± S.E.M. Data are analysed using ANOVA with a modified Bonferonni test, n = 4Ð8.

A similar fall in the force generation was seen in muscles of adult and old wild-type and HSP70 transgenic mice at 3 h following the contraction protocol (adult wild-type: 37 ± 6, adult HSP70: 38 ± 10, old wild-type: 42 ± 7, old HSP70: 29 ± 3 % of pre-exercise value). However, muscles of adult and old wild-type mice demonstrated a further loss of force generation at 3 days following the contraction protocol (adult: 24 ± 7 %, old: 27 ± 7 % of pre-exercise values), which was significantly (P < 0.05) lower than the value at 3 h following the contraction protocol. There was no evidence of a secondary loss of force in muscles of adult or aged HSP70 transgenic mice at this time point (adult: 37 ± 4, old: 38 ± 14). The maximum force generated by muscles of adult transgenic mice had recovered to pre-exercise values by 14 days following the contractions, whereas a significant (P < 0.05) deficit remained in the muscles of adult wild-type mice (HSP70: 85 ± 15 %, wild-type: 46 ± 10 % of pre-exercise value, P < 0.05). Muscles of adult wild-type mice had recovered to pre-exercise values by 28 days following the contraction protocol. The ability of muscles from old transgenic mice to recover following damage was maintained, whereas a significant (P < 0.05) deficit existed in muscles of old wild-type mice at 28 days following the contractile protocol (56 ± 7 % of pre-exercise value).

These data indicate that the diminished production of HSP70 in muscles of old mammals has a major effect on age-related functional deficits in muscle.

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

All procedures accord with current UK legislation.