Affordable Access

Publisher Website

Counteracting Age-Related Netrin-1 Signaling Insufficiency Ameliorates Endothelial Cell Senescence and Angiogenesis Impairment.

Authors
  • Yang, Zhen1, 2
  • Li, Han1, 2
  • Yan, Dan1, 2
  • Luo, Pengcheng1, 2
  • Guan, Yuqi1, 2
  • Luo, Mandi1, 2
  • Nie, Hao1, 2
  • Huang, Yi1, 2
  • Zhang, Le1, 2
  • Ruan, Lei1, 2
  • Yan, Jinhua1, 2
  • Zhang, Cuntai1, 2
  • 1 Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. , (China)
  • 2 Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. , (China)
Type
Published Article
Journal
The Journals of Gerontology Series A
Publisher
Oxford University Press
Publication Date
Feb 01, 2024
Volume
79
Issue
2
Identifiers
DOI: 10.1093/gerona/glad194
PMID: 37561046
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Senescent cells that accumulate are regarded as promising therapeutic targets. However, senolytic therapy failed to achieve satisfactory results. We previously discovered that young human plasma improved vascular endothelial cell senescence, and UNC5B might be a novel intervention target. Netrin-1, as a natural ligand of UNC5B, plays roles in multiple age-related vascular disorders, but its involvement in aging is still unclear. Here, we observed a significant decrease in plasma Netrin-1 levels in old healthy subjects compared to the young. In vivo, adeno-associated-virus-mediated delivery of Netrin-1 into aged mice significantly improved functional recovery in a model of hindlimb ischemia, promoted angiogenesis in ischemic tissues, and activated the endothelial nitric oxide synthase. Furthermore, we revealed that low-dose Netrin-1 recombinant protein significantly reduced senescence-associated-β-galactosidase-positive cells, inhibited the P53 pathway, promoted cell migration, increased tubule formation, and elevated nitric oxide production in senescent endothelial cells. However, UNC5B inhibition blocked the pro-angiogenesis effect of low-dose Netrin-1 on senescent cells or aortic rings. In summary, this study depicts that modulating Netrin-1 signaling can result in improved vascular health and Netrin-1 may have therapeutic potential for age-related ischemic diseases. © The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: [email protected].

Report this publication

Statistics

Seen <100 times