Vascular niches as the primary hotspots for cardiac aging

Aging is a major, yet unmodifiable, risk factor for cardiovascular disease, leading to vascular alterations, increased cardiac fibrosis, and inflammation, all of which contribute to impaired cardiac function. To investigate the spatial impact of aging, we applied an integrative approach combining single-nucleus RNA sequencing and spatial transcriptomics in 12-week-old and 18-month-old mice. We systematically mapped the aging heart and identified larger vessel-associated niches as key hotspots for activated macrophages and fibroblasts in aged hearts. These niches, surrounding arteries, were also enriched in senescent cells. Our findings suggest that the microenvironment around the vasculature is particularly susceptible to age-related changes and serves as a primary site for inflammation-driven aging so called \"inflammaging\". This study provides new insights into how aging reshapes cardiac cellular architecture, highlighting vessel-associated niches as potential therapeutic targets for age-related cardiac dysfunction.