Skeletal muscle mass and function progressively decline with ageing. This continual decline results in the development of sarcopenia and is a leading cause of mortality in older individuals. However, the molecular mechanisms driving this decline are not fully understood which prevents the development of pharmaceutical interventions. Proteins are key regulators of muscle function, driving both molecular and physical properties. Ubiquitylation is a post-transcriptional modification which has a widespread impact on the function of the proteome, regulating most biological processes in cells and tissues but well known for its role in protein degradation. We were interested in obtaining a comprehensive insight into age-related changes of proteins and their ubiquitin modifications to identify potential biomarkers of muscle decline. To do this we took the gastrocnemius complex muscle from young (6 month) and old (21-22 month) C57BL/6 male and female mice (n=3 from each sex), fractionated the lysate into soluble and insoluble proteins and analysed changes in the total proteome and ubiquitin-enriched proteome using quantitative mass spectrometry. Bioinformatics analysis of the proteomic dataset highlighted profound changes to the mitochondrial and sarcomere, along with a general decline in proteostasis in older muscle. Notably, we found sarcomeric proteins enriched in the soluble fraction of old muscle, many of which were ubiquitylated. We hypothesise that these proteins have been damaged and released from the sarcomere for ubiquitin-mediated degradation. Overall, this global protein profiling has provided new insight into age-related changes in skeletal muscle that likely contribute towards the loss of muscle mass and function. All animal procedures were approved by the Institutional Animal Care and Use Committee of the University of Iowa.