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Age-associated alterations of the hormone-secreting endocrine system cause organ dysfunction and disease states. However, the cell biology of endocrine tissue ageing remains poorly understood. Here, we perform comparative 3D imaging to understand age-related perturbations of the endothelial cell (EC) compartment in endocrine glands. Datasets of a wide range of markers highlight a decline in capillary and artery numbers, but not of perivascular cells in pancreas, testis and thyroid gland, with age in mice and humans. Further, angiogenesis and β-cell expansion in the pancreas are coupled by a distinct age-dependent subset of ECs. While this EC subpopulation supports pancreatic β cells, it declines during ageing concomitant with increased expression of the gap junction protein Gja1. EC-specific ablation of Gja1 restores β-cell expansion in the aged pancreas. These results provide a proof of concept for understanding age-related vascular changes and imply that therapeutic targeting of blood vessels may restore aged endocrine tissue function. This comprehensive data atlas offers over > 1,000 multicolour volumes for exploration and research in endocrinology, ageing, matrix and vascular biology.

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3D imaging, ageing, endocrine system, pancreas, vasculature, Adolescent, Adult, Aged, Aged, 80 and over, Aging, Animals, Blood Vessels, Endocrine Glands, Endocrine System, Endothelial Cells, Female, Humans, Imaging, Three-Dimensional, Insulin-Secreting Cells, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neovascularization, Pathologic, Pancreas, Testis, Thyroid Gland, Young Adult