Metabolites and Metabolic Functional Changes—Potential Markers for Endothelial Cell Senescence

Ya, Jingyuan; Whitby, Alison; Bayraktutan, Ulvi

Abstract

Accumulation of senescent endothelial cells (ECs) in vasculature represents a key step in the development of vascular aging and ensuing age-related diseases. Given that removal of senescent ECs may prevent disease and improve health and wellbeing, the discovery of novel biomarkers that effectively identify senescent cells is of particular importance. As crucial elements for biological pathways and reliable bioindicators of cellular processes, metabolites demand attention in this context. Using senescent human brain microvascular endothelial cells (HBMECs) displaying a secretory phenotype and significant morphological, nuclear, and enzymatic changes compared to their young counterparts, this study has shown that senescent HBMECs lose their endothelial characteristics as evidenced by the disappearance of CD31/PECAM-1 from interendothelial cell junctions. The metabolic profiling of young versus senescent HBMECs also indicates significant differences in glucose, glutamine, and fatty acid metabolism. The analysis of intracellular and secreted metabolites proposes L-proline, L-glutamate, NAD + , and taurine/hypotaurine pathway components as potential biomarkers. However, further studies are required to assess the value of these agents as potential biomarkers and therapeutic targets.

Citation

Ya, J., Whitby, A., & Bayraktutan, U. (2024). Metabolites and Metabolic Functional Changes—Potential Markers for Endothelial Cell Senescence. Biomolecules, 14(11), Article 1476. https://doi.org/10.3390/biom14111476

• Journal Article Type: Article
• Acceptance Date: Nov 18, 2024
• Online Publication Date: Nov 20, 2024
• Publication Date: Nov 20, 2024
• Deposit Date: Nov 20, 2024
• Publicly Available Date: Nov 20, 2024
• Journal: Biomolecules
• Electronic ISSN: 2218-273X
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 11
• Article Number: 1476
• DOI: https://doi.org/10.3390/biom14111476
• Keywords: endothelial cells; metabolomics; metabolites; aging; senescence; biomarkers; age-related disease
• Public URL: https://nottingham-repository.worktribe.com/output/42210930
• Publisher URL: https://www.mdpi.com/2218-273X/14/11/1476
• Additional Information: Received: 27 September 2024 Revised: 21 October 2024 Accepted: 18 November 2024; Academic Editor: Ruey-Bing Yang Copyright: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Article