High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging

Blood vessels provide supportive microenvironments for maintaining tissue functions. Age-associated vascular changes and their relation to tissue aging and pathology are poorly understood. Here, we perform 3D imaging of young and aging vascular beds. Multiple organs in mice and humans demonstrate an age-dependent decline in vessel density and pericyte numbers, while highly remodeling tissues such as skin preserve the vasculature. Vascular attrition precedes the appearance of cellular hallmarks of aging such as senescence. Endothelial VEGFR2 loss-of-function mice demonstrate that vascular perturbations are sufficient to stimulate cellular changes coupled with aging. Age-associated tissue-specific molecular changes in the endothelium drive vascular loss and dictate pericyte to fibroblast differentiation. Lineage tracing of perivascular cells with inducible PDGERB and NG2 Cre mouse lines demonstrated that increased pericyte to fibroblast differentiation distinguishes injury-induced organ fibrosis and zymosan-induced arthritis. To spur further discoveries, we provide a freely available resource with 3D vascular and tissue maps.

Automated summary

Blood vessels play a crucial role in supporting tissue functions, but age-associated vascular changes and their connection to tissue aging remains poorly understood. Vessel density and pericyte numbers decline with age in multiple organs, except highly remodeling tissues like the skin which preserve their vasculature. Molecular changes in the endothelium drive vascular loss and influence pericyte to fibroblast differentiation.