As life expectancy increases, age-related diseases are becoming more prevalent. While these conditions are traditionally studied in isolation, mounting evidence points to shared, systemic mechanisms underlying these conditions. Our research highlights the vasculature as a key player in organ homeostasis and repair, and a system shared across all organs—making its dysfunction potential driver of age-related pathologies.We demonstrate that manipulating VEGF signaling to counteract age-related microvascular rarefaction promotes comprehensive geroprotection, preserving organ function and delaying disease onset. Our findings also reveal a link between vascular rarefaction and altered RNA splicing. While hypoxia-driven and age-related changes in alternative RNA splicing have been studied independently, we propose a unifying mechanism that links the two. To explore this further, we also employ patient-derived organoids, which retain their biological age in culture, providing a robust in vitro platform to test anti-aging interventions.Our findings support a vascular theory of aging, identifying vascular health as a promising target to mitigate age-related diseases and promote healthier aging.
