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Article

Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells

1
Institute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University Jena, 07745 Jena, Germany
2
Leibniz Institute on Aging-Fritz Lipmann Institute, 07745 Jena, Germany
*
Author to whom correspondence should be addressed.
Current address: Center for Pandemic Vaccines and Therapeutics (ZEPAI), Paul Ehrlich Institute (PEI), 63225 Langen, Germany.
Academic Editors: Isabella Saggio and Romina Burla
Cells 2022, 11(14), 2213; https://doi.org/10.3390/cells11142213
Received: 27 May 2022 / Revised: 5 July 2022 / Accepted: 13 July 2022 / Published: 16 July 2022
(This article belongs to the Special Issue The Molecular Mechanism of Cellular Senescence)
Vascular aging is based on the development of endothelial dysfunction, which is thought to be promoted by senescent cells accumulating in aged tissues and is possibly affected by their environment via inflammatory mediators and oxidative stress. Senescence appears to be closely interlinked with changes in cell metabolism. Here, we describe an upregulation of both glycolytic and oxidative glucose metabolism in replicative senescent endothelial cells compared to young endothelial cells by employing metabolic profiling and glucose flux measurements and by analyzing the expression of key metabolic enzymes. Senescent cells exhibit higher glycolytic activity and lactate production together with an enhanced expression of lactate dehydrogenase A as well as increases in tricarboxylic acid cycle activity and mitochondrial respiration. The latter is likely due to the reduced expression of pyruvate dehydrogenase kinases (PDHKs) in senescent cells, which may lead to increased activity of the pyruvate dehydrogenase complex. Cellular and mitochondrial ATP production were elevated despite signs of mitochondrial dysfunction, such as an increased production of reactive oxygen species and extended mitochondrial mass. A shift from glycolytic to oxidative glucose metabolism induced by pharmacological inhibition of PDHKs in young endothelial cells resulted in premature senescence, suggesting that alterations in cellular glucose metabolism may act as a driving force for senescence in endothelial cells. View Full-Text
Keywords: aging; endothelial cell; replicative senescence; glucose metabolism; lactate; lactate dehydrogenase; pyruvate dehydrogenase kinase; dichloroacetate aging; endothelial cell; replicative senescence; glucose metabolism; lactate; lactate dehydrogenase; pyruvate dehydrogenase kinase; dichloroacetate
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MDPI and ACS Style

Stabenow, L.K.; Zibrova, D.; Ender, C.; Helbing, D.L.; Spengler, K.; Marx, C.; Wang, Z.-Q.; Heller, R. Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells. Cells 2022, 11, 2213. https://doi.org/10.3390/cells11142213

AMA Style

Stabenow LK, Zibrova D, Ender C, Helbing DL, Spengler K, Marx C, Wang Z-Q, Heller R. Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells. Cells. 2022; 11(14):2213. https://doi.org/10.3390/cells11142213

Chicago/Turabian Style

Stabenow, Leonie K., Darya Zibrova, Claudia Ender, Dario L. Helbing, Katrin Spengler, Christian Marx, Zhao-Qi Wang, and Regine Heller. 2022. "Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells" Cells 11, no. 14: 2213. https://doi.org/10.3390/cells11142213

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