A vascular-centered approach for promoting healthy aging

Aging embodies multiple cellular processes but their governing hierarchies are poorly understood. Here we examined the proposition that loss of vascular-tissue communication is a critical upstream driver of physiological aging at large. Counteracting age-related VEGF signaling insufficiency via modest increase of circulating VEGF levels prevented capillary loss and secured proper tissue oxygenation in aging. Preservation of a young-like vascular homeostasis, not only led to unprecedented lifespan extension, but also to healthier aging. This was manifested in a leaner body composition, preservation of mitochondrial function, metabolic flexibility and thermogenic capacity, reduced inflammaging and reduced endothelial cell senescence. Aging-associated morbidities alleviated included steatosis. sarcopenia, osteoporosis and increased cancer incidence. The study suggests harnessing VEGF-mediated preservation of vascular homeostasis as a yet uncharted modality for conferring comprehensive geroprotection and multifaceted healthspan increase.