Sialic acids (Sia) are widely expressed as terminal monosaccharides on eukaryotic glycoconjugates. They are involved in many cellular functions, such as cell-cell interaction and signal recognition. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), which catalyses the first two steps of Sia biosynthesis in the cytosol. In this study we analysed sialylation of muscles in wild type (C57Bl/6 GNE (+/+)) and heterozygous GNE-deficient (C57Bl/6 GNE (+/-)) mice. We measured a significantly lower performance in the initial weeks of a treadmill exercise in C57Bl/6 GNE (+/-) mice compared to wild type C57Bl/6 GNE (+/+)animals. Membrane bound Sia of C57Bl/6 GNE (+/-) mice were reduced by 33-53% at week 24 and by 12-15% at week 80 in comparison to C57Bl/6 GNE (+/+)mice. Interestingly, membrane bound Sia concentration increased with age of the mice by 16-46% in C57Bl/6 GNE (+/+), but by 87-207% in C57Bl/6 GNE (+/-). Furthermore we could identify specific morphological changes in aged muscles. Here we propose that increased Sia concentrations in muscles are a characteristic feature of ageing and could be used as a marker for age-related changes in muscle.