Why the heart loses elasticity in old age and becomes more susceptible to disease is still only partially understood. Researchers at Goethe University Frankfurt, the Cardiopulmonary Institute (CPI) and the German Centre for Cardiovascular Research (DZHK) have now shown that the crucial processes take place primarily in the vicinity of blood vessels. These so-called vascular niches are the sites where inflammation, cell ageing and remodeling processes in the heart tissue begin.
For the study, which was published in Circulation Research, the team led by first author David Rodriguez Morales and last author Stefanie Dimmeler analysed the hearts of young and old mice using the most modern single-cell and tissue technologies. They identified eleven different microenvironments in the heart tissue that differ in their cell composition and activity. The areas close to the blood vessels showed particularly significant changes: ageing cells accumulate there, sending out inflammatory signals and causing the tissue to harden.
Inflammation hotspots
‘Our data suggests that ageing of the heart begins, in a sense, in the blood vessels,’ says David Rodriguez Morales. ‘These niches act like small hotspots that trigger inflammation and remodelling processes, which then spread to the entire organ.’
The team also tested whether this process could be slowed down. In old mice treated with senolytics – substances that specifically remove ageing cells – certain inflammatory cells in the vascular niches decreased. This could indicate that therapies targeting these microenvironments could protect the heart in old age.
‘Ageing is not a uniform process that affects the entire heart,’ says Stefanie Dimmeler. ‘Rather, it seems to originate in specific areas. This insight opens up new possibilities for targeted intervention where the damage occurs.’
The study thus provides a basis for better understanding age-related changes in the cardiovascular system in the future and influencing them therapeutically.
Original work:
Rodriguez Morales D, Larcher V, Ruz Jurado M, et al. Vascular Niches Are the Primary Hotspots in Cardiac Aging. Circ Res. Published online October 15, 2025. doi:10.1161/CIRCRESAHA.125.327060
