PhD defence S. (Soroush) Mohammadi Jouabadi

Below is a brief summary of the dissertation:

Blood vessels age throughout life. With age, they can become stiffer and less able to widen, even before clear signs of atherosclerosis appear. This “vascular aging” increases the risk of cardiovascular disease, kidney problems and cognitive decline.

This thesis combined population research with laboratory experiments to understand why blood vessels age and whether existing medicines could slow or partly reverse this process. Data from the Rotterdam Study showed that inflammation and blood fats explain only a small part of the relationship between age and changes in the arteries. This suggests that several biological processes act together.

Genetic and observational analyses indicated that pathways affected by metformin, a widely used diabetes medicine, may be linked to lower arterial stiffness. In accelerated-aging mouse models and isolated arteries, metformin and the anti-inflammatory medicine colchicine improved the ability of blood vessels to relax, reduced arterial stiffness and limited harmful changes in the vessel wall. These effects were associated with improved protective signalling in the vessel lining, less inflammation and reduced damage to collagen and elastin.

The findings show the value of combining evidence from people, genetics and experimental models. They also suggest that existing medicines may have potential for treating vascular aging. However, the results do not yet prove that these drugs should be used for this purpose in patients; clinical studies are needed first.