Department of Developmental Biology and Cancer Research Faculty of Medicine, The Hebrew University
Head of the Hadassah Organoid Center, The Hadassah Medical Organization, Ein Kerem, Jerusalem, ISRAEL

Aging: Microvascular dysfunction at the driver’s seat

Host: S. Zacchigna

The increase in lifespan witnessed during the last century is unfortunately associated with more years of compromised health, as improvements in health-span have not kept pace. Interventions aiming at delaying the onset of age-associated diseases are urgently needed. Current research is focused on targeting cellular pathways recognized as “hallmarks” of aging including cell senescence, mitochondria dysfunction, and more recently epigenetic reprogramming. However, recent studies have challenged the notion of uniform aging, revealing distinct aging rates and trajectories for various organs. This also might suggest a hierarchical relationship among organs. Considering the intricate relationship of the vasculature with all other organs, we propose that vascular aging serves as a critical upstream driver contributing to the deterioration of numerous other organs. Our findings present compelling evidence that VEGF-based vascular manipulations, which counteracts age-associated microvascular rarefaction, is sufficient to confer holistic geroprotection. Furthermore, our recent findings indicate that maintaining youthful VEGF levels also delays thymic atrophy, positively impacting the immune system, and reinforcing its role in overall health enhancement. This innovative approach underscores the potential of vascular-based strategies to extend both lifespan and healthspan – at least in mice!


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