Stroke, Academic Unit of Mental Health and Clinical Neurosciences, School of Medicine, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
Children's Brain Tumor Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK.
Biomolecules. 2024 Nov 20;14(11):1476. doi: 10.3390/biom14111476.
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.
衰老内皮细胞（ECs）在血管中的积累是血管衰老和随后的与年龄相关疾病发展的关键步骤。鉴于清除衰老的 ECs 可能预防疾病并改善健康和幸福感，因此发现有效识别衰老细胞的新型生物标志物尤为重要。作为生物途径的关键要素和细胞过程的可靠生物标志物，代谢物在这种情况下需要引起关注。本研究使用表现出分泌表型以及与年轻对应物相比具有显著形态、核和酶学变化的衰老人脑微血管内皮细胞（HBMEC）表明，衰老的 HBMEC 失去了其内皮特性，这表现在 CD31/PECAM-1 从内皮细胞连接处消失。与年轻的 HBMEC 相比，衰老的 HBMEC 的代谢组学分析也表明在葡萄糖、谷氨酰胺和脂肪酸代谢方面存在显著差异。细胞内和分泌代谢物的分析提出 L-脯氨酸、L-谷氨酸、NAD 和牛磺酸/次牛磺酸途径成分作为潜在的生物标志物。然而，需要进一步的研究来评估这些物质作为潜在生物标志物和治疗靶点的价值。
