Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells
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 chan...
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MDPI AG
2022-07-01
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| author | Leonie K. Stabenow Darya Zibrova Claudia Ender Dario L. Helbing Katrin Spengler Christian Marx Zhao-Qi Wang Regine Heller |
| author_facet | Leonie K. Stabenow Darya Zibrova Claudia Ender Dario L. Helbing Katrin Spengler Christian Marx Zhao-Qi Wang Regine Heller |
| author_sort | Leonie K. Stabenow |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T12:05:33Z |
| format | Article |
| id | doaj.art-4e79ea5e59b34386911a38e499fdd768 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T12:05:33Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4e79ea5e59b34386911a38e499fdd7682023-11-30T22:58:44ZengMDPI AGCells2073-44092022-07-011114221310.3390/cells11142213Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial CellsLeonie K. Stabenow0Darya Zibrova1Claudia Ender2Dario L. Helbing3Katrin Spengler4Christian Marx5Zhao-Qi Wang6Regine Heller7Institute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University Jena, 07745 Jena, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University Jena, 07745 Jena, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University Jena, 07745 Jena, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University Jena, 07745 Jena, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University Jena, 07745 Jena, GermanyLeibniz Institute on Aging-Fritz Lipmann Institute, 07745 Jena, GermanyLeibniz Institute on Aging-Fritz Lipmann Institute, 07745 Jena, GermanyInstitute of Molecular Cell Biology, Jena University Hospital, Friedrich Schiller University Jena, 07745 Jena, GermanyVascular 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.https://www.mdpi.com/2073-4409/11/14/2213agingendothelial cellreplicative senescenceglucose metabolismlactatelactate dehydrogenase |
| spellingShingle | Leonie K. Stabenow Darya Zibrova Claudia Ender Dario L. Helbing Katrin Spengler Christian Marx Zhao-Qi Wang Regine Heller Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells Cells aging endothelial cell replicative senescence glucose metabolism lactate lactate dehydrogenase |
| title | Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells |
| title_full | Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells |
| title_fullStr | Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells |
| title_full_unstemmed | Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells |
| title_short | Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells |
| title_sort | oxidative glucose metabolism promotes senescence in vascular endothelial cells |
| topic | aging endothelial cell replicative senescence glucose metabolism lactate lactate dehydrogenase |
| url | https://www.mdpi.com/2073-4409/11/14/2213 |
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