Fig. 1.

Global and tissue-specific changes of the healthy aging endothelium. Middle: Core aging-associated changes in the endothelial landscape, identified in single-cell transcriptomics studies across different tissues (human and/or primate and/or mouse), include a decreased abundance of ECs (in comparison to other cell types) with increasing age, typically via a reduction in capillary/microvascular subtype abundance. Gene signatures associated with immunoregulatory processes and inflammation are generally increased in aging ECs across organs and tissues. Tissue-specific changes of the endothelium with increasing age are indicated in circled boxes next to each tissue. Phenotypes shared among two–three tissues are indicated at the bottom, including elevated expression of senescence-associated gene signatures (FRS, heart, kidney, lung), either a reduced (muscle, heart) or increased (brain, FRS) expression of angiogenic gene signatures, reduced expression of DNA repair signatures (skin, FRS), fewer interactions between ECs and other cell types (skin, FRS), increased transcriptional noise (brain, heart, lung, skin), and increased expression of VWF (lung, brain) or IL7 (heart, lung), as specified for each tissue by colored icons. EC = endothelial cell; ECM = extracellular matrix; DEG = differentially expressed gene; FRS = female reproductive system; Klfs = Krüppel-like factors; TF = transcription factor