Ageing is accompanied by a reduction in skeletal muscle mass and strength which leads to instability, increased risk of falls and an inability to perform everyday tasks. In addition, skeletal muscle of old mammals is more susceptible to exercise-induced damage and has a markedly impaired ability to fully regenerate following damage. The mechanisms underlying these age-related functional defects are unclear although several reports suggest that deficits may be associated with accumulation of oxidative damage. Muscles of young individuals can adapt to prevent damage following exercise. One of the major components of this adaptation is the increased production of heat shock proteins (HSPs). This induction of HSPs is impaired in muscles of old rodents (Vasilaki et al, 2006). Studies from our laboratory have demonstrated that this inability to produce HSPs plays a role in the development of age-related functional deficits. Lifelong overexpression of HSP70 in skeletal muscles of mice resulted in protection against some aspects of exercise- induced muscle damage, but most strikingly, resulted in efficient and successful recovery of muscles of old mice following a severe damaging exercise (McArdle et al, 2004). Muscles of old wild type mice demonstrated biochemical changes consistent with increased oxidative damage and an inability to activate other redox-sensitive transcription factors such as NFkB and AP-1 (Broome et al, 2006). In contrast, these changes were not evident in muscles of old HSP70 overexpressors (Broome et al, 2006). Studies examining the effect of overexpression of other HSPs demonstrate cytoprotection against other aspects of contraction-induced damage, demonstrating the importance of different components of the stress response in cytoprotection. The mechanisms by which increased HSP content confers protection appears to be due to a reduced accumulation of oxidative damage and maintenance of the ability of muscles to activate other redox-responsive transcription factors. Further evidence for this comes from examination of muscles from SOD1 null mice which demonstrate aberrant activation of NFkB and an accelerated loss of muscle mass and function with age (Muller et al, 2006).