The UK is projected to become a hyper-aged society in 2030 with 36% of its population over 55. The early diagnosis and treatment for tissue degeneration are one of the most pressing challenges in healthcare. Osteoarthritis is a form of cartilage degeneration and the most common musculoskeletal disorder. It is affecting nearly one third of adults over 45 years old and causing more than £850 million direct cost in NHS, plus £3.2 billion indirect cost for downtime and community care. By targeting the cartilage, this project will establish a fundamental link between highly sensitive structural biomarkers in tissue degeneration and biomechanical functionality, therefore providing the possibility of identifying new targets for early diagnosis and novel therapies. This will be achieved by combining 1) advanced imaging technique for the subtle structural changes in the cartilage, 2) micromechanical loading to visualise the structural responses under different cartilage conditions, and 3) numerical simulation for analysing the integrity of tissues and the mechanobiological communication of cells at different ages. The outcomes of this project will provide experimental and simulational evidence to inform the clinical translation of the imaging technique for early diagnosis of osteoarthritis, allow quantitative evaluation of the treatment effectiveness of anti-osteoarthritis drugs, and facilitate the development of novel cellular and regenerative therapies. The approach established in this project will lead to a new toolkit of studying biomechanics-centred dysfunctions in a wide range of tissues.