A vascular-centered view on aging and rejuvenation

Loss of vascular homeostasis in old age, primarily due to blood vessels loss is bound to adversely affect vascular-tissue communication in ways conducive to functional failure of multiple organs. A failure to maintain adequate microvascular density was attributed to age-related VEGF signaling insufficiency caused by accumulation of neutralizing VEGF decoy receptors at old age. Securing a youthful level of VEGF signaling via compensatory mild increase of circulatory VEGF prevented microcirculatory loss, improved organ perfusion and function, and conferred comprehensive geroprotection, culminating in both dramatic lifespan and healthspan extension. Healthier aging was evidenced by favourable metabolism and body composition and by amelioration of aging-associated pathologies, such as hepatic steatosis, sarcopenia, osteoporosis, chronic inflammation (“inflammaging”), and increased tumour burden. Delayed thymus involution in VEGF-treated mice also ‘rejuvenated’ the T-cells landscape. These findings thus provide a solid basis for the previously proposed “vascular theory of aging” and suggests harnessing vascular rejuvenation as a yet uncharted modality for promoting healthier aging.