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High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging
File(s)
Author(s)
Chen, Junyu
Sivan, Unnikrishnan
Tan, Sin Lih
Lippo, Luciana
De Angelis, Jessica
Type
Journal Article
Abstract
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 PDGFRβ 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.
Date Issued
2021-02-03
Date Acceptance
2020-12-23
Citation
Science Advances, 2021, 7 (6), pp.1-17
URI
DOI
ISSN
2375-2548
Publisher
American Association for the Advancement of Science
Start Page
1
End Page
17
Journal / Book Title
Science Advances
Volume
7
Issue
6
Copyright Statement
© 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33536212
PII: 7/6/eabd7819
Publication Status
Published
Coverage Spatial
United States