Multiscale mechanobiological synergies in vascular homeostasis, ageing and reju...
Whilst 30% of EU citizens will be over 65 and 10% over 80 by 2050, the healthspan accounts for only 80% of the total life expectancy according to Eurostat, due to the high prevalence of disabling diseases related to the age-induce...
Whilst 30% of EU citizens will be over 65 and 10% over 80 by 2050, the healthspan accounts for only 80% of the total life expectancy according to Eurostat, due to the high prevalence of disabling diseases related to the age-induced arterial stiffening. The current paradigm in medicine is to palliate these diseases with sophisticated devices. In JuvenTwin, I propose a complete shift of paradigm by combatting the mechanobiological effects of vascular ageing. Vascular rejuvenation faces many challenges that have only been explored by molecular biologists. My ambition is to address these challenges with a high-risk approach relying on multiscale digital twins and enabling to simulate and screen effective rejuvenation treatments. My hypothesis, already supported by preliminary results, is that this can be achieved by doping the synergistic effects of mechano-regulation in human arteries, which are gradually compromised with vascular ageing. JuvenTwin’s four specific objectives are: 1/ Decipher how ageing affects cell phenotypes and the signalling pathways of mechano-regulation, 2/ Assess the effects of ageing on the mechanical interactions between cells and their matrix, 3/ Simulate computationally the multiscale synergies participating to patient-specific vascular mechano-regulation and finally 4/ Take the control of mechanobiology in aged arteries using small molecule inhibitors and cell mechanical stimulations. With my team, we will reach these objectives by developing two completely novel methodologies: a 4D high-resolution strain mapper and a micromechanical computational model simulating the dynamical interactions of 100,000 vascular cells in patient-specific arteries. Our interdisciplinary approach combining digital spatial transcriptomics, laser interferometry and neural networks will be of very high-gain for discovering therapies against the adverse mechanobiological effects of vascular ageing, potentially reaching the pre-clinical stage at the horizon 2030.ver más
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