Ageing is accompanied by several "age-associated' diseases, most of them involving tissue disorganization associated with a loss of tissue elasticity, with multiple physiological, mechanical and social consequences. The goal of this proposal is to target the ageing of elastic tissue to cope with ageing, or at least some manifestations of ageing. As the mechanisms that govern correct elastogenesis during development, which are lost in adulthood and ageing, are still unknown, and as it is also unknown how to reactivate these processes, the project introduces a coordinated action to find "positive modulators" (protection against degradation and post-translational modification, re-induction of optimal elastogenesis) of elastic tissue ageing.The originality of the proposal lies in the Coordination of strategies that will define: i) rodent and tissue-equivalent models to study the impact of therapeutic approaches on elastic tissue ageing, ii) the development of diverse elastic fibre-derived peptides - proteoglycan conjugates based on the elastic fibre components structure and its alterations with age, in order to protect or delay elastic fibre degradation or post-translational modification, and iii) the development of strategies to assess neosynthesis of elastic tissues and to define biomarkers at the cross-roads between ageing and elastic tissue ageing. Assays on cells from humans displaying genetically-based "exaggerated" ageing will be used as indicators of the effectiveness of the selected "modulators".The expected impacts should be a breakthrough on skin and vessel ageing treatments with a special interest with the improvement of chronic vein insufficiency and, longer term, other disorders of joints, arteries and macula and the improvement of healing. The project brings together 12 participants with complementary expertise from 6 different countries, including basic scientists, clinicians and three SMEs. Ethical, gender and standardisation aspects are also included.
|
