The reduction in muscle mass and strength that occur during ageing can have a major impact on the quality of life of older individuals. Older people demonstrate reduced mobility which in turn leads to loss of independence, falls and social isolation. These changes occur partly because a large proportion of the muscle fibres are lost, but also the fibres that are retained are weak. It is currently unknown how muscle fibres are lost during ageing, but when these fibres are lost, the nerves that normally control the activity of these fibres are also lost. Age-related changes in the interactions between nerves and muscles are poorly understood but appear to play a major role in development of muscle weakness and physical frailty in older people.We have studied age-related structural changes in neuromuscular junctions (NMJs) using thy1-YFP transgenic mice that only express YFP in neuronal cells and permit ready localisation of the motor neurons and NMJs and staining with α-bungarotoxin to visualise the acetylcholine receptors (AChR). Comparison of NMJs from adult and old mice revealed a variety of age-related structural alterations, swellings, partial or complete withdrawal of axons from some postsynaptic motor endplates, and fragmentation of the postsynaptic organisation.We have also examined the pattern of structural changes in motor neurons and NMJs following a protocol of damaging lengthening contractions to determine whether this process was defective in muscles of old mice. Structural changes in NMJs as well as the loss and regrowth of peripheral motor neurons were examined by fluorescence microscopy. Three days after injury, muscles from adult and old mice showed widespread necrosis. By 28 days, muscles from adult mice appeared histologically normal, whereas muscles from old mice showed multiple small atrophic fibres and fibres with central nuclei. Major disruption of the NMJs was seen at 3 days following damage in both adult and old mice, followed by re-innervation of the muscle that was completed by 28 days in adult mice (96% of the NMJs in EDL muscles from adult mice appeared to be normal with only 2% showing full denervation), but which remained sub-optimal in muscles of old mice.Thus, data indicate that skeletal muscle ageing influences muscle regeneration, muscle innervation and neuromuscular junction plasticity.