The role of mitochondrial ROS in the aging brain
Open accessAbstract
The brain is the most complex human organ, consuming more energy than any other tissue in proportion to its size. It relies heavily on mitochondria to produce energy and is made up of mitotic and postmitotic cells that need to closely coordinate their metabolism to maintain essential bodily functions. During aging, damaged mitochondria that produce less ATP and more reactive oxygen species (ROS) accumulate. The current consensus is that ROS cause oxidative stress, damaging mitochondria and resulting in an energetic crisis that triggers neurodegenerative diseases and accelerates aging. However, in model organisms, increasing mitochondrial ROS (mt ROS) in the brain extends lifespan, suggesting that ROS may participate in signaling that protects the brain. Here, we summarize the mechanisms by which mt ROS are produced at the molecular level, how different brain cells and regions produce different amounts of mt ROS, and how mt ROS levels change during aging. Finally, we critically discuss the possible roles of ROS in aging as signaling molecules and damaging agents, addressing whether age‐associated increases in mt ROS are a cause or a consequence of aging.
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Mitochondrial dysfunction plays a pivotal role in the aging process, affecting cellular function including energy metabolism and oxidative stress.
“Mitochondrial dysfunction plays a pivotal role in the aging process, affecting various aspects of cellular function, including energy metabolism and oxidative stress.”
From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Stefanatos and Sanz, 2018
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López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734 · see citing works
Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
Scherz‐Shouval, R., Shvets, E., Fass, E., Shorer, H., Gil, L., & Elazar, Z. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601623 · Cited by 2,101 · see citing works
Cellular senescence mediates fibrotic pulmonary disease
Schafer, M. J., White, T. A., Iijima, K., Haak, A. J., Ligresti, G., Atkinson, E. J., Oberg, A. L., Birch, J., Salmonowicz, H., Zhu, Y., et al. (2017) · Nature Communications · doi:10.1038/ncomms14532 · Cited by 1,613 · cited 1× · see citing works
“further confirmed, the existence of senolytic drugs that have been shown effective to correct agerelated alterations in other organs such as the liver [85] or lung [86] could also be effective in the”
BackgroundSchulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., & Ristow, M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.011 · Cited by 1,209 · see citing works
Ageing, neurodegeneration and brain rejuvenation
Wyss-Coray, T. (2016) · Nature · doi:10.1038/nature20411 · Cited by 1,147 · see citing works
The role of mitochondria in aging
Bratic, A., & Larsson, N.-G. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64125 · Cited by 1,087 · see citing works
Cellular senescence drives age-dependent hepatic steatosis
Ogrodnik, M., Miwa, S., Tchkonia, T., Tiniakos, D., Wilson, C. L., Lahat, A., Day, C. P., Burt, A., Palmer, A., Anstee, Q. M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15691 · Cited by 1,044 · see citing works
Complex iii releases superoxide to both sides of the inner mitochondrial membrane
Muller, F. L., Liu, Y., & Van Remmen, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407715200 · Cited by 1,036 · see citing works
Feedback between p21 and reactive oxygen production is necessary for cell senescence
Passos, J. F., Nelson, G., Wang, C., Richter, T., Simillion, C., Proctor, C. J., Miwa, S., Olijslagers, S., Hallinan, J., Wipat, A., et al. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.5 · Cited by 1,019 · cited 2× · see citing works
“Subsequently, p21 induces mitochondrial dysfunction and more ROS that are required to maintain DNA damage and senescence [84].”
BackgroundCombating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets
Drummond, G. R., Selemidis, S., Griendling, K. K., & Sobey, C. G. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3403 · Cited by 899 · see citing works
Mitochondria are required for pro-ageing features of the senescent phenotype
Correia‐Melo, C., Marques, F. D., Anderson, R., Hewitt, G., Hewitt, R., Cole, J., Carroll, B. M., Miwa, S., Birch, J., Merz, A., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201592862 · Cited by 796 · see citing works
A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury
Chouchani, E. T., Pell, V. R., James, A. M., Work, L. M., Saeb-Parsy, K., Frezza, C., Krieg, T., & Murphy, M. P. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.009 · Cited by 752 · see citing works
Overexpression of Atg5 in mice activates autophagy and extends lifespan
Pyo, J.-O., Yoo, S.-M., Ahn, H.-H., Nah, J., Hong, S.-H., Kam, T.-I., Jung, S., & Jung, Y.-K. (2013) · Nature Communications · doi:10.1038/ncomms3300 · Cited by 721 · see citing works
Jurk, D., Wang, C., Miwa, S., Maddick, M., Korolchuk, V., Tsolou, A., Gonos, E. S., Thrasivoulou, C., Jill Saffrey, M., Cameron, K., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00870.x · Cited by 598 · see citing works
Scialò, F., Fernández-Ayala, D. J., & Sanz, A. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00428 · Cited by 517 · see citing works
Self-citationNuclear DNA damage signalling to mitochondria in ageing
Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.14 · Cited by 387 · see citing works
Mitochondrial ROS produced via reverse electron transport extend animal lifespan
Scialò, F., Sriram, A., Fernández-Ayala, D., Gubina, N., Lõhmus, M., Nelson, G., Logan, A., Cooper, H. M., Navas, P., Enríquez, J. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.009 · Cited by 371 · see citing works
Self-citationDaiber, A. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.01.032 · Cited by 347 · see citing works
Barja, G. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5148 · Cited by 290 · see citing works
Brand, M. D., Goncalves, R. L. S., Orr, A. L., Vargas, L., Gerencser, A. A., Borch Jensen, M., Wang, Y. T., Melov, S., Turk, C. N., Matzen, J. T., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.012 · Cited by 228 · cited 2× · see citing works
“Finally, novel antioxidant molecules that prevent electron leak from specific sites within the respiratory complexes have been developed and tested in human cells as well as mouse and fly models [15, 16].”
Background
Flagged first, then by citations
Cited by
Sorted by citations
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Reiter, R., Tan, D., Rosales-Corral, S., Galano, A., Zhou, X., & Xu, B. (2018) · Molecules · doi:10.3390/molecules23020509 · Cited by 393 · see citing works
Kelmer Sacramento, E., Kirkpatrick, J. M., Mazzetto, M., Baumgart, M., Bartolome, A., Di Sanzo, S., Caterino, C., Sanguanini, M., Papaevgeniou, N., Lefaki, M., et al. (2020) · Molecular Systems Biology · doi:10.15252/msb.20209596 · Cited by 236 · see citing works
Mossad, O., Batut, B., Yilmaz, B., Dokalis, N., Mezö, C., Nent, E., Nabavi, L. S., Mayer, M., Maron, F. J. M., Buescher, J. M., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01027-3 · Cited by 241 · see citing works
The mitochondrial permeability transition: Nexus of aging, disease and longevity
Rottenberg, H., & Hoek, J. B. (2021) · Cells · doi:10.3390/cells10010079 · Cited by 94 · see citing works
Calcium, Bioenergetics, and Parkinson’s Disease
Zampese, E., & Surmeier, D. J. (2020) · Cells · doi:10.3390/cells9092045 · Cited by 79 · see citing works
Ye, M.-J., & Meng, N. (2021) · Bioengineered · doi:10.1080/21655979.2021.1954742 · Cited by 43 · see citing works
Aging promotes an increase in mitochondrial fragmentation in astrocytes
Araujo, A. P. B., Vargas, G., Hayashide, L. D. S., Matias, I., Andrade, C. B. V., de Carvalho, J. J., Gomes, F. C. A., & Diniz, L. P. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1496163 · Cited by 43 · see citing works
- Authors
- Stefanatos, R., & Sanz, A.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Sanz, Alberto
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2017-11-15
- Volume
- 592
- Issue
- 5
- Pages
- 743-758
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2767505663
- Cited by
- 358
- References
- 21
- Citations by year
- 2026: 21 · 2025: 45 · 2024: 49 · 2023: 55 · 2022: 63 · 2021: 57 · 2020: 38 · 2019: 18 · 2018: 12
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- European Research Council (260632)
- Biotechnology and Biological Sciences Research Council (BB/M023311/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial reactive oxygen species, brain aging, oxidative stress, mitochondrial dysfunction, neurodegeneration, lifespan extension, ROS signaling, brain energy metabolism
- MeSH terms
- Adenosine Triphosphate, Aging, Animals, Brain, Energy Metabolism, Humans, Mitochondria, Signal Transduction, Reactive Oxygen Species, Neurodegenerative Diseases
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