The DOI matches its Crossref record; 244 of the 244 references it cites were found in a registry or an index.
The redox stress hypothesis of aging
Open accessAbstract
The main objective of this review is to examine the role of endogenous reactive oxygen/nitrogen species (ROS) in the aging process. Until relatively recently, ROS were considered to be potentially toxic by-products of aerobic metabolism, which, if not eliminated, may inflict structural damage on various macromolecules. Accrual of such damage over time was postulated to be responsible for the physiological deterioration in the postreproductive phase of life and eventually the death of the organism. This "structural damage-based oxidative stress" hypothesis has received support from the age-associated increases in the rate of ROS production and the steady-state amounts of oxidized macromolecules; however, there are increasing indications that structural damage alone is insufficient to satisfactorily explain the age-associated functional losses. The level of oxidative damage accrued during aging often does not match the magnitude of functional losses. Although experimental augmentation of antioxidant defenses tends to enhance resistance to induced oxidative stress, such manipulations are generally ineffective in the extension of life span of long-lived strains of animals. More recently, in a major conceptual shift, ROS have been found to be physiologically vital for signal transduction, gene regulation, and redox regulation, among others, implying that their complete elimination would be harmful. An alternative notion, advocated here, termed the "redox stress hypothesis," proposes that aging-associated functional losses are primarily caused by a progressive pro-oxidizing shift in the redox state of the cells, which leads to the overoxidation of redox-sensitive protein thiols and the consequent disruption of the redox-regulated signaling mechanisms.
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“The alternative “redox stress hypothesis” [215] instead proposes that impairments in physiologic function are due to an age-related “pro-oxidizing shift” in the redox state of cells that results in the over-oxidation of redox-sensitive thiol groups within the cysteine residues of proteins, resulting in the impairment of cellular signaling pathways.”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [215]
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“A variety of phenomena have been proposed to contribute to this age-related heightened inflammatory state including redox stress [46], immuno- and endocrine senescence [47, 48], DNA damage [49], epigenetic modification [50], and a distortion of gut microbial homeostasis [51] that is associated with increased levels of circulating endotoxin [42].”
From Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis (2018) · cites this paper as [46]
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Rea, I. M., Gibson, D. S., McGilligan, V., McNerlan, S. E., Alexander, H. D., & Ross, O. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00586 · Cited by 1,267
Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130
The role of mitochondria in aging
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Oxidative stress response and Nrf2 signaling in aging
Zhang, H., Davies, K. J. A., & Forman, H. J. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.05.036 · Cited by 804
Sivandzade, F., Prasad, S., Bhalerao, A., & Cucullo, L. (2019) · Redox Biology · doi:10.1016/j.redox.2018.11.017 · Cited by 639
Metadata
- Authors
- Sohal, R. S., & Orr, W. C.
- Affiliations
- University of Southern California (US)
- Southern Methodist University (US)
- Corresponding author
- Sohal, Rajindar S.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 52
- Issue
- 3
- Pages
- 539-555
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC3267846
- OpenAlex
- W1986589519
- Cited by
- 473
- References
- 244
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 21 · 2023: 24 · 2022: 24 · 2021: 24 · 2020: 29 · 2019: 32 · 2018: 34 · 2017: 35 · 2016: 33 · 2015: 46 · 2014: 57 · 2013: 43 · 2012: 32
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01 AG15122, R01 AG 17077, R01 AG13563, R01-AG 7657, R01 AG17526, R01AG020715, R01AG007657, R01AG013563, R01 AG20715, R01AG017526, R01AG015122, R01AG017077)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- aging, reactive oxygen species, reactive nitrogen species, oxidative stress, redox regulation, protein thiol oxidation, antioxidant defense, lifespan extension, redox signaling
- MeSH terms
- Aging, Animals, Cell Differentiation, Humans, Oxidation-Reduction, Oxygen Consumption, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, Reactive Nitrogen Species, Growth and Development
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