Ferroptosis and ageing
https://doi.org/10.37489/2587-7836-2025-1-17-26
EDN: VWHUHM
Abstract
Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxidation. Since its initial description, it has garnered significant attention due to its implications in various diseases, including cancer, neurodegeneration, and ischemia-reperfusion injury. The ageing process is characterized by a progressive decline in cellular function and increased susceptibility to oxidative damage, both of which intersect with ferroptosis pathways. This review explores the intricate relationship between ferroptosis and ageing, focusing on molecular mechanisms, the role of iron metabolism, implications in age-related diseases, and potential therapeutic strategies. By understanding the interplay between ferroptosis and ageing, researchers can uncover novel targets for promoting healthy ageing and mitigating age-associated disorders.
About the Authors
A. A. Garanin
Ivanovo State Medical University of MOH of Russia
Russian Federation
Russian Federation
Alexey A. Garanin — Associate Professor of the Department of Pharmacology of the FSBEI HE «Ivanovo SMU» of MOH of Russia.
Ivanovo
T. E. Bogacheva
Ivanovo State Medical University of MOH of Russia
Russian Federation
Russian Federation
Tatiana E. Bogacheva — PhD, Cand. Sci. (Med.), Associate Professor of the Department of Pharmacology of the FSBEI HE IvSMA MOH Russia.
Ivanovo
O. A. Gromova
Ivanovo State Medical University of MOH of Russia
Russian Federation
Russian Federation
Olga A. Gromova — Professor of the Department of Pharmacology FSBEI HE «Ivanovo SMU» of MOH of Russia; Dr. Sci. (Med.), Professor, Leading researcher FRC CSC RAS.
Ivanovo; Moscow
References
1. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012 May 25;149(5):1060-72. doi: 10.1016/j.cell.2012.03.042.
2. Di Micco R, Krizhanovsky V, Baker D, et al. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol. 2021 Feb;22(2):75-95. doi: 10.1038/s41580-020-00314-w.
3. Fang X, Ardehali H, Min J, Wang F. The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease. Nat Rev Cardiol. 2023 Jan;20(1):7-23. doi: 10.1038/s41569-022-00735-4.
4. Reichert CO, de Freitas FA, Sampaio-Silva J, et al. Ferroptosis Mechanisms Involved in Neurodegenerative Diseases. Int J Mol Sci. 2020 Nov 20;21(22):8765. doi: 10.3390/ijms21228765.
5. Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 2021 Apr;22(4):266-282. doi: 10.1038/s41580-020-00324-8.
6. Zhang Y, Xin L, Xiang M, et al. The molecular mechanisms of ferroptosis and its role in cardiovascular disease. Biomed Pharmacother. 2022 Jan;145:112423. doi: 10.1016/j.biopha.2021.112423.
7. Stockwell BR. Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications. Cell. 2022 Jul 7;185(14):2401-2421. doi: 10.1016/j.cell.2022.06.003.
8. Nemeth E, Ganz T. Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis. Int J Mol Sci. 2021 Jun 17;22(12):6493. doi: 10.3390/ijms22126493.
9. Li L, Wang K, Jia R, et al. Ferroportin-dependent ferroptosis induced by ellagic acid retards liver fibrosis by impairing the SNARE complexes formation. Redox Biol. 2022 Oct;56:102435. doi: 10.1016/j.redox.2022.102435.
10. Liao P, Wang W, Wang W, et al. CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell. 2022 Apr 11;40(4):365-378.e6. doi: 10.1016/j.ccell.2022.02.003.
11. Liang D, Minikes AM, Jiang X. Ferroptosis at the intersection of lipid metabolism and cellular signaling. Mol Cell. 2022 Jun 16;82(12):2215-2227. doi: 10.1016/j.molcel.2022.03.022.
12. Rochette L, Dogon G, Rigal E, et al. Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis. Int J Mol Sci. 2022 Dec 27;24(1):449. doi: 10.3390/ijms24010449.
13. Minami JK, Morrow D, Bayley NA, et al. CDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis. Cancer Cell. 2023 Jun 12;41(6):1048-1060.e9. doi: 10.1016/j.ccell.2023.05.001.
14. Xue Q, Yan D, Chen X, et al. Copper-dependent autophagic degradation of GPX4 drives ferroptosis. Autophagy. 2023 Jul;19(7):1982-1996. doi: 10.1080/15548627.2023.2165323.
15. Liu Y, Wan Y, Jiang Y, et al. GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment. Biochim Biophys Acta Rev Cancer. 2023 May;1878(3):188890. doi: 10.1016/j.bbcan.2023.188890.
16. Li D, Wang Y, Dong C, et al. CST1 inhibits ferroptosis and promotes gastric cancer metastasis by regulating GPX4 protein stability via OTUB1. Oncogene. 2023 Jan;42(2):83-98. doi: 10.1038/s41388-022-02537-x.
17. Liu J, Kang R, Tang D. Signaling pathways and defense mechanisms of ferroptosis. FEBS J. 2022 Nov;289(22):7038-7050. doi: 10.1111/febs.16059
18. Chen X, Yu C, Kang R, et al. Cellular degradation systems in ferroptosis. Cell Death Differ. 2021 Apr;28(4):1135-1148. doi: 10.1038/s41418-020-00728-1.
19. Tian Y, Tian Y, Yuan Z, et al. Iron Metabolism in Aging and Age-Related Diseases. Int J Mol Sci. 2022 Mar 25;23(7):3612. doi: 10.3390/ijms23073612.
20. Zhao T, Guo X, Sun Y. Iron Accumulation and Lipid Peroxidation in the Aging Retina: Implication of Ferroptosis in Age-Related Macular Degeneration. Aging Dis. 2021 Apr 1;12(2):529-551. doi: 10.14336/AD.2020.0912.
21. Costa I, Barbosa DJ, Benfeito S, et al. Molecular mechanisms of ferroptosis and their involvement in brain diseases. Pharmacol Ther. 2023 Apr;244:108373. doi: 10.1016/j.pharmthera.2023.108373.
22. Qiu B, Zandkarimi F, Bezjian CT, et al. Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis. Cell. 2024 Feb 29;187(5):1177-1190.e18. doi: 10.1016/j.cell.2024.01.030.
23. Anandhan A, Dodson M, Shakya A, et al. NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8. Sci Adv. 2023 Feb 3;9(5):eade9585. doi: 10.1126/sciadv.ade9585.
24. Chen GH, Song CC, Pantopoulos K, et al. Mitochondrial oxidative stress mediated Fe-induced ferroptosis via the NRF2-ARE pathway. Free Radic Biol Med. 2022 Feb 20;180:95-107. doi: 10.1016/j.freerad-biomed.2022.01.012.
25. Niu B, Liao K, Zhou Y, et al. Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy. Biomaterials. 2021 Oct;277:121110. doi: 10.1016/j.biomaterials.2021.121110.
26. Yan D, Wu Z, Qi X. Ferroptosis-related metabolic mechanism and nanoparticulate anticancer drug delivery systems based on ferroptosis. Saudi Pharm J. 2023 Apr;31(4):554-568. doi: 10.1016/j.jsps.2023.02.008.
27. Gromova OA, Torshin II, Chuchalin AG. [Ferritin as a biomarker of aging: geroprotective peptides of standardized human placental hydrolysate. A review]. Ter Arkh. 2024 Sep 14;96(8):826-835. Russian. doi: 10.26442/00403660.2024.08.202811.
28. Torshin IY, Gromova OA, Tikhonova OV, Chuchalin AG. [Molecular mechanisms of the effect of standardized placental hydrolysate peptides on mitochondria functioning]. Ter Arkh. 2023 Dec 28;95(12):1133-1140. Russian. doi: 10.26442/00403660.2023.12.202494.
29. Tian R, Abarientos A, Hong J, et al. Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis. Nat Neurosci. 2021 Jul;24(7):1020-1034. doi: 10.1038/s41593-021-00862-0.
Review
For citations:
Garanin A.A., Bogacheva T.E., Gromova O.A. Ferroptosis and ageing. Pharmacokinetics and Pharmacodynamics. 2025;(1):17-26. (In Russ.) https://doi.org/10.37489/2587-7836-2025-1-17-26. EDN: VWHUHM
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