Decreased blood vessel density and endothelial cell subset dynamics during ageing of the endocrine system

EMBO J. 2021 Jan 4;40(1):e105242. doi: 10.15252/embj.2020105242. Epub 2020 Nov 20.

Abstract

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.

Keywords: 3D imaging; ageing; endocrine system; pancreas; vasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Animals
  • Blood Vessels
  • Endocrine Glands / physiology
  • Endocrine System / physiology*
  • Endothelial Cells / physiology*
  • Female
  • Humans
  • Imaging, Three-Dimensional / methods
  • Insulin-Secreting Cells / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neovascularization, Pathologic / pathology
  • Pancreas / physiology
  • Testis / physiology
  • Thyroid Gland / physiology
  • Young Adult