Three core mechanisms drive vascular aging: epigenetic drift, chronic low-grade inflammation particularly through the IL-1β pathway, and accumulating senescent cells. These processes create a cascade where deteriorating blood vessels become the central driver of age-related multimorbidity rather than just another symptom of aging.
This mechanistic clarity opens compelling therapeutic windows. SGLT2 inhibitors, originally diabetes drugs, show vascular protective effects beyond glucose control. Mitochondrial-targeted antioxidants like MitoQ directly address cellular energy dysfunction in vessel walls. Most intriguingly, senolytics—drugs that eliminate senescent cells—represent a fundamentally new approach to rejuvenating aged vasculature rather than merely slowing decline.
The translational challenge remains formidable. Animal models poorly predict human vascular responses, drug delivery to vessel walls proves difficult, and clinical trials lack validated biomarkers for vascular health. The authors advocate for liquid biopsy markers and precision medicine approaches tailored to individual vascular aging profiles. This represents a paradigm shift from treating cardiovascular disease symptoms to preventing the vascular deterioration that underlies multiple age-related conditions simultaneously.
