Multiscale mechanobiological synergies in vascular homeostasis, ageing and rejuvenation

Introduction

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. This is due to the high prevalence of disabling diseases related to age-induced arterial stiffening. The current paradigm in medicine is to palliate these diseases with sophisticated devices.

Project Overview

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, enabling the simulation and screening of effective rejuvenation treatments.

Hypothesis

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.

Specific Objectives

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 in patient-specific vascular mechano-regulation.
4. Take control of mechanobiology in aged arteries using small molecule inhibitors and cell mechanical stimulations.

Methodology

With my team, we will reach these objectives by developing two completely novel methodologies:

• A 4D high-resolution strain mapper.
• A micromechanical computational model simulating the dynamical interactions of 100,000 vascular cells in patient-specific arteries.

Interdisciplinary Approach

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. This research aims to potentially reach the pre-clinical stage by the horizon of 2030.