Age-related loss of skeletal muscle mass and function is a major cause of loss of mobility, increased frailty and falls in the elderly and impacts profoundly on the quality of life of older people. Modified reactive oxygen species (ROS) generation has been implicated in the mechanisms by which muscle function is lost with increasing age. ROS are increased in skeletal muscles of adult mice following a period of isometric contractions and this is associated with adaptive increases in transcription of a number of cytoprotective proteins in muscle including the heat shock proteins (HSPs). In contrast ROS generation and the ability to activate this adaptive stress response are modified in skeletal muscle of old mice, which also demonstrate a chronic activation of NFκB, associated with a pro-inflammatory environment. Transgenic studies have demonstrated that this blunted adaptive response plays a key role in development of age-related functional deficits. Lifelong overexpression of cytoprotective HSPs results in improved muscle function and a reduction in the accumulation of markers of oxidative stress in muscles of old mice. Studies have demonstrated that mice lacking Cu,Zn superoxide dismutase showed an accelerated loss of skeletal muscle and bone mass and function and examination of adaptive responses in muscles of adult Sod1−/− mice show aberrant DNA binding activity of NFκB similar to that observed in muscles of old WT mice. These data demonstrate a role for aberrant ROS generation in age-related loss of muscle mass and function, that the development of age-related muscle weakness and atrophy are not inevitable and strengthen the hypothesis of the involvement of failed adaptive responses in the development of these deficits.
This work was funded by Research into Ageing, BBSRC, MRC, Arthritis Research UK and National Institutes of Health (USA).
18 May 2013 - 22 May 2013