Oxidants, oxidative stress and the biology of ageing

Finkel, Toren; Holbrook, Nikki J.

doi:10.1038/35041687

Cited by 9,413Genetics, Aging, and Longevity in Model OrganismsRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

Oxidants, oxidative stress and the biology of ageing

Finkel, Toren, Holbrook, Nikki J.·2000·Nature

DOI 10.1038/35041687

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Abstract

Living in an oxygenated environment has required the evolution of effective cellular strategies to detect and detoxify metabolites of molecular oxygen known as reactive oxygen species. Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span.

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Crossref · 10.1038/35041687

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During aging and neurodegeneration, there is a decrease in normal antioxidant and anti-inflammatory defense mechanisms, making the brain more susceptible to detrimental effects of oxidative stress.
“During aging and neurodegeneration, there is a decrease in normal antioxidant and anti-inflammatory defense mechanisms, making the brain more susceptible to the detrimental effects of oxidative stress [44,45,46].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [45]
Most neurological disorders such as Alzheimer's disease, Parkinson's disease, inflammatory injuries and senility are the result of age-linked inflammation and/or oxidative stress increase.
“Indeed, most neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), inflammatory injuries and senility are the result of age-linked inflammation and/or oxidative stress increase [44,45].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [45]
Inflammation and oxidative stress play a fundamental role in the onset and progression of neurodegenerative diseases.
“There is considerably strong evidence to clarify that inflammation and oxidative stress play a fundamental role in the onset and progression of neurodegenerative diseases [45],”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [45]
A complex antioxidant defense system including endogenous and exogenous antioxidants protects cells from ROS-induced toxicity.
“A complex antioxidant defense system, including both endogenous and exogenous antioxidants, protect cells from ROS-induced toxicity (Finkel and Holbrook 2000).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Finkel and Holbrook 2000
One of the hallmarks of aging is elevated oxidative stress and inflammation.
“One of the hallmarks of aging is elevated oxidative stress and inflammation (Finkel and Holbrook, 2000).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Finkel and Holbrook, 2000

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Nitric Oxide and Peroxynitrite in Health and Disease
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The Role of Oxidative Stress in Parkinson's Disease
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Mitochondria are required for antigen-specific t cell activation through reactive oxygen species signaling
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Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction
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SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α
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Role of oxidative stress in Alzheimer’s disease
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A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
Lee, S. S., Lee, R. Y. N., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G. (2003) · Nature Genetics · doi:10.1038/ng1056 · Cited by 969 · see citing works
DNA Repair, Genome Stability, and Aging
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Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans
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Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives
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α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies
Wong, Y. C., & Krainc, D. (2017) · Nature Medicine · doi:10.1038/nm.4269 · Cited by 897 · see citing works
Body size, energy metabolism and lifespan
Speakman, J. R. (2005) · Journal of Experimental Biology · doi:10.1242/jeb.01556 · Cited by 914 · see citing works
The aging of the immune system
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An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations
Kregel, K. C., & Zhang, H. J. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00327.2006 · Cited by 883 · see citing works
Aβ Oligomers Induce Neuronal Oxidative Stress through an N-Methyl-D-aspartate Receptor-dependent Mechanism That Is Blocked by the Alzheimer Drug Memantine
De Felice, F. G., Velasco, P. T., Lambert, M. P., Viola, K., Fernandez, S. J., Ferreira, S. T., & Klein, W. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607483200 · Cited by 882 · see citing works
Molecular mechanisms of ROS production and oxidative stress in diabetes
Newsholme, P., Cruzat, V. F., Keane, K. N., Carlessi, R., & de Bittencourt, P. I. H. (2016) · Biochemical Journal · doi:10.1042/bcj20160503c · Cited by 878 · see citing works
Redox Regulation of Forkhead Proteins Through a <i>p66shc</i> -Dependent Signaling Pathway
Nemoto, S., & Finkel, T. (2002) · Science · doi:10.1126/science.1069004 · Cited by 818 · see citing works
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Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression
Neumann, C. A., Krause, D. S., Carman, C. V., Das, S., Dubey, D. P., Abraham, J. L., Bronson, R. T., Fujiwara, Y., Orkin, S. H., & Van Etten, R. A. (2003) · Nature · doi:10.1038/nature01819 · Cited by 801 · see citing works
Evaluation of antioxidant capacity and total phenolic content of different fractions of selected microalgae
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Resolving the Role of Lipoxygenases in the Initiation and Execution of Ferroptosis
Shah, R., Shchepinov, M. S., & Pratt, D. A. (2018) · ACS Central Science · doi:10.1021/acscentsci.7b00589 · Cited by 782 · see citing works
Reactive oxygen species in cardiovascular disease
Sugamura, K., & Keaney (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.004 · Cited by 769 · see citing works
Small Molecule Modulators of <scp>K</scp> eap1‐ <scp>N</scp> rf2‐ <scp>ARE</scp> Pathway as Potential Preventive and Therapeutic Agents
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Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation
Owusu-Ansah, E., & Banerjee, U. (2009) · Nature · doi:10.1038/nature08313 · Cited by 742 · see citing works
Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila
Simonsen, A., Cumming, R. C., Brech, A., Isakson, P., Schubert, D. R., & Finley, K. D. (2008) · Autophagy · doi:10.4161/auto.5269 · Cited by 716 · see citing works
Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix
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SIRT3, a Mitochondrial Sirtuin Deacetylase, Regulates Mitochondrial Function and Thermogenesis in Brown Adipocytes
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Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology
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Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling
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Senescent cells as a source of inflammatory factors for tumor progression
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Preparation of antioxidant enzymatic hydrolysates from α-Lactalbumin and β-Lactoglobulin. Identification of Active Peptides by HPLC-MS/MS.
Hernández-Ledesma, B., Dávalos, A., Bartolomé, B., & Amigo, L. (2005) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf048626m · Cited by 634 · see citing works
The Mammalian Target of Rapamycin (mTOR) Pathway Regulates Mitochondrial Oxygen Consumption and Oxidative Capacity
Schieke, S. M., Phillips, D., McCoy, J. P., Aponte, A. M., Shen, R.-F., Balaban, R. S., & Finkel, T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603536200 · Cited by 623 · see citing works
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Postmitotic neurons develop a p21‐dependent senescence‐like phenotype driven by a DNA damage response
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
Widespread Proteome Remodeling and Aggregation in Aging C. elegans
Walther, D. M., Kasturi, P., Zheng, M., Pinkert, S., Vecchi, G., Ciryam, P., Morimoto, R. I., Dobson, C. M., Vendruscolo, M., Mann, M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.03.032 · Cited by 569 · see citing works
Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis
Grootaert, M. O. J., Moulis, M., Roth, L., Martinet, W., Vindis, C., Bennett, M. R., & De Meyer, G. R. Y. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy007 · Cited by 606 · see citing works
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Smoliga, J. M., Baur, J. A., & Hausenblas, H. A. (2011) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201100143 · Cited by 594 · see citing works
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JNK Activity in Somatic Stem Cells Causes Loss of Tissue Homeostasis in the Aging Drosophila Gut
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Grandmothers and the evolution of human longevity
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Ageing, age-related diseases and oxidative stress: What to do next?
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The role of nuclear lamin B1 in cell proliferation and senescence
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Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS
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Circulating Glycotoxins and Dietary Advanced Glycation Endproducts: Two Links to Inflammatory Response, Oxidative Stress, and Aging
Uribarri, J., Cai, W., Peppa, M., Goodman, S., Ferrucci, L., Striker, G., & Vlassara, H. (2007) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/62.4.427 · Cited by 570 · see citing works
Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice
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Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases
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Nitrogen dioxide and carbonate radical anion: two emerging radicals in biology
Augusto, O., Bonini, M. G., Amanso, A. M., Linares, E., Santos, C. C. X., & De Menezes, S. L. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00786-4 · Cited by 555 · see citing works
Linking oxidative stress to inflammation: Toll-like receptors
Gill, R., Tsung, A., & Billiar, T. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.01.006 · Cited by 553 · see citing works
Vascular Cell Senescence: Contribution to Atherosclerosis
Minamino, T., & Komuro, I. (2007) · Circulation Research · doi:10.1161/01.res.0000256837.40544.4a · Cited by 542 · see citing works
The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging
Yu, C., & Xiao, J.-H. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6635460 · Cited by 537 · see citing works
Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study
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Chronic Oxidative Stress Compromises Telomere Integrity and Accelerates the Onset of Senescence in Human Endothelial Cells
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A Meta-analysis of oxidative stress markers in depression
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Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis
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The redox stress hypothesis of aging
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Oxidative stress and aberrant signaling in aging and cognitive decline
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eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues
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Comparing genomic expression patterns across species identifies shared transcriptional profile in aging
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Ageing and diabetes: implications for brain function
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Authors: Finkel, T., & Holbrook, N. J.
Affiliations: National Institutes of Health (US)
Corresponding author: Finkel, Toren
Holbrook, Nikki J.
ORCID: Finkel, Toren
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2000-11
Volume: 408
Issue: 6809
Pages: 239-247
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35041687
OpenAlex: W2101861123
Cited by: 9,413
References: 104
Citations by year: 2026: 194 · 2025: 337 · 2024: 330 · 2023: 384 · 2022: 413 · 2021: 447 · 2020: 488 · 2019: 502 · 2018: 487 · 2017: 510 · 2016: 464 · 2015: 428 · 2014: 475 · 2013: 457 · 2012: 478
FWCI: 10.25
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords: oxidizing agents, oxidative stress, aging, reactive oxygen species, lifespan, oxygen metabolism, cellular detoxification
MeSH terms: Aging, Animals, Energy Intake, Humans, Longevity, Signal Transduction, Oxidants, Cellular Senescence, Reactive Oxygen Species, Oxidative Stress

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