Proliferation dynamics of organotypic vascular endothelium during aging

Abstract Healthy blood vessels are vital for organismal health. Blood vessel-lining endothelial cells (ECs) can self-replicate to maintain vascular homeostasis, yet the age-related dynamics of EC proliferation remain elusive. Employing cumulative labeling of proliferating ECs, we here present a temporal map of organotypic changes in endothelial proliferation at different stages of mouse life [juvenile (J), 1-month-old; young adult (YA), 4-month-old; old adult (OA), 14-month-old]. Comparative analyses of 12 different organs revealed a tissue-specific pattern of age-related changes in endothelial proliferation capacity. Contrary to the prevailing notion, the majority of analyzed vascular beds retained their proliferative capacity during aging. Intriguingly, lung ECs manifested increased proliferation, whereas adipose, colon, and liver tissues displayed reduced EC proliferation during aging. Together, the data provide a vascular reference framework, highlighting a high degree of organ specificity in the self-renewal capacity of differentiated ECs and uncovering the influence of organismal aging on EC proliferation.