The knee joint is a complex weight bearing joint that has a high incidence of degenerative change and knee OA. Consequently, there is a need to develop a greater understanding of factors that may affect knee articular cartilage and influence long term health of the knee joint. The overall aim of this thesis was to specifically investigate the effect of ageing and physical activity on several serum biomarkers that have been found to have a different profile among individuals with degenerative knee conditions such as OA. These biomarkers included: serum COMP, which is understood to be a marker of cartilage degeneration or metabolism; serum HA, which is also understood to be both a marker of cartilage degeneration and synovial inflammation; serum lubricin, which is understood to be a marker of joint lubrication; and finally, femoral cartilage thickness assessed by ultrasound (US), which provides a morphological measurement of the articular cartilage. Firstly, in Chapter 4, the feasibility of measuring femoral cartilage thickness using US was determined. This study demonstrated high intra-tester reliability, measurement precision, and revealed that femoral cartilage thickness has a large variability in healthy individuals across a range of ages. In a subsequent cross-sectional study (Chapter 5), results indicated that ageing does not inevitably result in degenerative change of articular cartilage in healthy males. Moreover, physical activity was not associated with any adverse changes to joint markers, and instead, was associated with greater lateral condyle cartilage thickness in this cohort. Chapters 6 and 7 specifically explored acute joint loading. Acute exercise increased serum lubricin and COMP with no change in serum HA. The increase in serum COMP and lubricin suggests an increase in cartilage metabolism and joint lubrication, respectively. However, somewhat surprisingly this response did not differ between weight bearing and non-weight bearing exercise. The follow up study compared aerobic exercise with resistance training. Despite substantial differences in the loading magnitude and frequency between lower body resistance exercise and walking exercise, both exercise modalities resulted in a similar response in serum biomarkers. There was also no difference between the exercise response in both healthy male and female individuals. Overall, this research has provided new evidence to suggest that both healthy ageing and physical activity are not associated with adverse changes to the articular cartilage. Moreover, while acute exercise typically results in a significant increase in both serum COMP and lubricin, neither exercise modality nor gender appears to alter the response to acute loading.