Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease
Abstract
:1. Introduction
1.1. Cellular Senescence
1.2. The Senescence—Associated Secretory Phenotype (SASP)
1.3. Telomeres and Senescence
1.4. Telomere Dysfunction Regulates Mitochondrial Function and ROS and Vice Versa
1.5. Dietary Factors and the Regulation of Nicotinamide Adenine Dinucleotide (NAD+), Telomere and Mitochondrial Dysfunction and Its Relationship to Senescence
2. Senescent Cell Metabolism
2.1. Glycolysis and Pyruvate
2.2. Energy Regulation in Oncogene-Induced Senescence
2.3. Energy Regulation in Replicative Senescence
2.4. Unbiased Metabolomic Screens of Senescent Cells
2.5. Do Senescent Cells Exhibit a Reverse TCA Cycle?
2.6. The Relationship of the Extracellular Senescence Metabolome to the Internal Senescence Metabolome
3. The Role of p53 in Fibroblast Senescence and Metabolism
P53 Decline in Classical Genotoxic SIPS May Be Associated with a Shift towards Glycolysis and the PPP
4. The Extracellular Senescence Metabolome and the Identification of Extracellular Citrate Accumulation as a Common Feature of Replicative Senescence and Senescence-Induced by Irreparable DNA Damage: Evidence for Cell Type Specificity
5. Citrate Transport and Its Role in Ageing and Disease
5.1. Citrate in the Diet and Its Potential Effect on Senescence and the SASP
5.2. Citrate Import by SLC13A5/I’m Not Dead Yet (INDY)
5.3. Citrate Export and Its Upregulation in Senescence and Fibroblast Activation
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Mycielska, M.E.; James, E.N.; Parkinson, E.K. Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease. Int. J. Mol. Sci. 2022, 23, 3652. https://doi.org/10.3390/ijms23073652
Mycielska ME, James EN, Parkinson EK. Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease. International Journal of Molecular Sciences. 2022; 23(7):3652. https://doi.org/10.3390/ijms23073652
Chicago/Turabian StyleMycielska, Maria Elzbieta, Emma Naomi James, and Eric Kenneth Parkinson. 2022. "Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease" International Journal of Molecular Sciences 23, no. 7: 3652. https://doi.org/10.3390/ijms23073652