Extending life and health spans of mice by targeting their vasculature

Means to delay or attenuate development of aging-associated frailties and pathologies are greatly needed given the continual increase in lifespan. Considering the multiple homeostatic functions of the vasculature together with its evident functional deterioration with age, we hypothesize that vascular aging is a primary cause of organ aging at large. We show that a moderate increase of circulating levels of VEGF from early adulthood and onwards, is sufficient to confer generalized geroprotection by virtue of preventing microvascular rarefaction in old mice and securing proper tissue perfusion. Remarkably, VEGF treatment not only results in unprecedented degree of lifespan extension, but also considerably improves healthspan by delaying major aging-associated functional deterioration across multiple organs including sarcopenia, liver steatosis and osteoporosis. Particularly interesting is the maintenance of a “young” metabolism in VEGF-treated old mice, characterized by increased metabolic flexibility, improved glucose tolerance, decreased abdominal white fat accumulation despite similar food intake and exercise, accompanied by increased beige/brown fat thermogenesis. Importantly, VEGF-treated mice exhibit a lower propensity to develop spontaneous tumors, associated with a lower degree of “inflammaging”.

Altogether, these findings support the hypothesis that vascular aging is a primary cause of physiological aging and suggests its negation as a holistic geroprotective approach.