Le projet est axé sur le développement d'outils technologiques de haut niveau combinant des approches biologiques, biomécaniques et d'imagerie des tissus au cours du processus de vieillissement.
Integrative tissue ageing approach
Leader Work package : M.H. Lafage-Proust
Contexte et objectifs
Ageing affects the function of mineralised and soft tissues such as cartilage, bone, muscle, arteries and skin. Ageing deteriorates extracellular matrix (ECM) production, composition and maintenance by the cells which affects tissue capacity to adapt and respond to various environmental stimuli including mechanical stimuli. Mechanical properties of the ageing tissues are thus altered through either increased turnover or increased cross-linking of ECM. Reciprocally, ECM and the mechanical and biochemical processes it is subject to, affect the behavior of the residing cells including stem cells.
By mediating mechanotransduction and hosting growth factors, ECM regulates cell fate and growth, mediates signals for cell proliferation or apoptosis and also influences blood vessels and nerves in aging tissues. In this context the objectives of this work are to develop a multiscale integrative approach of the mechanical age-related deterioration of tissues.
For this purpose we will :
- elaborate standardized tools to characterise the mechanical properties of ageing tissues at the nano-, micro- and millimetre levels,
- correlate mechanical parameters obtained from the various tissues analysed (cartilage, skin bone and muscle),
- find common processes that would characterise stages in the ECM mechanical deterioration in these tissues.
This innovative approach should allow to define general characteristics of mechanics of ageing tissues, to further understand the relationships between impaired mechanics and loss of tissue function and maybe predict the mechanical behavior of one specific tissue from data obtained from another tissue.
The underlying role of ECM damage in this age-related decline in function will be assessed. Should drugs for the general prevention of the ageing process be available (such as anti-oxidants, telomerase stimulators or inhibitors of farnesylation like bisphosphonates) their systemic effects on the mechanical behavior of the targeted tissues would be then performed.
These objectives will be achieved through tight collaborations between the research teams involved in the IVTV project which will provide data obtained from the tissues analysed : cartilage, bone, muscle skin and arteries. Standardization of mechanical tests and experimental procedures will be requested.