The DOI matches its Crossref record; 39 of the 41 references it cites were found in a registry or an index.
Redox analysis of human plasma allows separation of pro-oxidant events of aging from decline in antioxidant defenses
Abstract
Oxidative stress is a component of diseases and degenerative processes associated with aging. However, no means are available to assess causative oxidative events separately from decline in function of protective antioxidant systems. Previous studies show that ongoing oxidative processes maintain plasma cysteine/cystine redox at a value that is more oxidized than the antioxidant glutathione/glutathione disulfide (GSH/GSSG) system, suggesting that redox analysis of these plasma thiols could allow separate evaluation of an increase in oxidative events from a decline in antioxidant function. The present study uses measurement of cysteine/cystine and GSH/GSSG redox in plasma of 122 healthy individuals aged 19-85 years to determine whether thiol-disulfide redox changes occur with age. The results show a linear oxidation of cysteine/cystine redox state with age at a rate of 0.16 mV/year over the entire age span. In contrast, GSH/GSSG redox was not oxidized prior to 45 years and subsequently was oxidized at a nearly linear rate of 0.7 mV/year. These data suggest that there is a continuous, linear increase in oxidative events throughout adult life but that the capacity of the GSH antioxidant system is maintained until 45 years and then declines rapidly. The data further suggest that redox states of cysteine/cystine and GSH/GSSG provide an approach to clinically distinguish between increased causative oxidative events and decreased GSH antioxidant function. In principle, such analyses can be used to assess efficacy of intervention strategies against oxidative stress prior to or early after onset of clinical symptoms in aging and age-related disease.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The Cys/CySS ratio tends to become even more oxidized with aging, smoking, diabetes, and obesity (198, 302).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [198]
Citations
Cites
The Free Radical Theory of Aging Matures
BECKMAN, K. B., & AMES, B. N. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.2.547 · Cited by 3,879
Oxidative stress and gene regulation
Allen, R. G., & Tresini, M. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00242-7 · Cited by 1,321
Redox Regulation of Cellular Signalling
Kamata, H., & Hirata, H. (1999) · Cellular Signalling · doi:10.1016/s0898-6568(98)00037-0 · Cited by 1,162
Oxidation-reduction potentials of organic systems
(1960) · Journal of the Franklin Institute · doi:10.1016/0016-0032(60)90644-x · Cited by 889
[11] Redox potential of GSH/GSSG couple: Assay and biological significance
Jones, D. P. (2002) · Methods in Enzymology · doi:10.1016/s0076-6879(02)48630-2 · Cited by 812
Self-citationLevine, R. L. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00765-7 · Cited by 676
Oxidative damage and protection of the RPE
Cai, J., Nelson, K. C., Wu, M., Sternberg, P., & Jones, D. P. (2000) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(99)00009-9 · Cited by 628
Self-citationRedox state of glutathione in human plasma
Jones, D. P., Carlson, J. L., Mody, V. C., Cai, J., Lynn, M., & Sternberg, P. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00275-0 · Cited by 587
Self-citationSamiec, P. S., Drews‐Botsch, C., Flagg, E. W., Kurtz, J. C., Sternberg, P., Reed, R. L., & Jones, D. P. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00286-4 · Cited by 497
Self-citationGlutathione measurement in human plasma
Jones, D. P., Carlson, J. L., Samiec, P. S., Sternberg, P., Mody, V. C., Reed, R. L., & Brown, L. A. S. (1998) · Clinica Chimica Acta · doi:10.1016/s0009-8981(98)00089-8 · Cited by 485
Self-citationOxidative modification of proteins during aging
Levine, R. L., & Stadtman, E. R. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00135-8 · Cited by 466
Properties and Biological Activities of Thioredoxins
Powis, G., & Montfort, W. R. (2001) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.261 · Cited by 449
Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects.
Delori, F. C., Goger, D. G., & Dorey, C. K. (2001) · PubMed · Cited by 424
Human studies related to protein oxidation: protein carbonyl content as a marker of damage.
Chevion, M., Berenshtein, E., & Stadtman, E. R. (2000) · PubMed · Cited by 400
Manganese superoxide dismutase in disease
MacMillan-Crow, L. A., & Cruthirds, D. L. (2001) · Free Radical Research · doi:10.1080/10715760100300281 · Cited by 371
Glutathione redox potential in response to differentiation and enzyme inducers
Kirlin, W. G., Cai, J., Thompson, S. A., Dı́az, D., Kavanagh, T. J., & Jones, D. P. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00145-8 · Cited by 359
Self-citationFunctions of Glutathione in Liver and Kidney
Sies, H., & Wendel, A. (1978) · Proceedings in life sciences · doi:10.1007/978-3-642-67132-6 · Cited by 351
Plasma antioxidants and longevity: a study on healthy centenarians
Mecocci, P., Polidori, M. C., Troiano, L., Cherubini, A., Cecchetti, R., Pini, G., Straatman, M., Monti, D., Stahl, W., Sies, H., et al. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00246-x · Cited by 306
Mechanisms of L-Cysteine Neurotoxicity
Janáky, R., Varga, V., Hermann, A., Saransaari, P., & Oja, S. S. (2000) · Neurochemical Research · doi:10.1023/a:1007616817499 · Cited by 292
Protein disulfide isomerase: The multifunctional redox chaperone of the endoplasmic reticulum
Noiva, R. (1999) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.1999.0319 · Cited by 279
Role of the Liver in Interorgan Homeostasis of Glutathione and Cyst(e)ine
Ookhtens, M., & Kaplowitz, N. (1998) · Seminars in Liver Disease · doi:10.1055/s-2007-1007167 · Cited by 211
A Mitochondrial Paradigm for Degenerative Diseases and Ageing
Wallace, D. C. (2001) · Novartis Foundation symposium · doi:10.1002/0470868694.ch20 · Cited by 210
Antioxidant regulation of genes encoding enzymes that detoxify xenobiotics and carcinogens
Dhakshinamoorthy, S., Long, D. J., & Jaiswal, A. K. (2001) · Current topics in cellular regulation · doi:10.1016/s0070-2137(01)80009-1 · Cited by 203
Distribution of oxidized and reduced forms of glutathione and cysteine in rat plasma
Lash, L. H., & Jones, D. P. (1985) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(85)90065-7 · Cited by 193
Self-citationReduction-potential of Glutathione
Rost, J., & Rapoport, S. M. (1964) · Nature · doi:10.1038/201185a0 · Cited by 172
Jonas, C. R., Puckett, A. B., Jones, D. P., Griffith, D. P., Szeszycki, E. E., Bergman, G. F., Furr, C. E., Tyre, C., Carlson, J. L., Galloway, J. R., et al. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/72.1.181 · Cited by 168
Self-citationRedox modulation of the NMDA receptor
Choi, Y., & Lipton, S. A. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000638 · Cited by 166
Immunohistochemical and ELISA Assays for Biomarkers of Oxidative Stress in Aging and Diseasea
Onorato, J. M., Thorpe, S. R., & Baynes, J. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09909.x · Cited by 141
Glutathione Therapy: From Prodrugs to Genes
Anderson, M. E., & Luo, J. (1998) · Seminars in Liver Disease · doi:10.1055/s-2007-1007174 · Cited by 140
Age-related changes in oxidative damage to lipids and DNA in rat skin
Tahara, S., Matsuo, M., & Kaneko, T. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00257-8 · Cited by 78
Epidermal growth factor receptor is modulated by redox through multiple mechanisms
Kamata, H., Shibukawa, Y., Oka, S., & Hirata, H. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01194.x · Cited by 76
Lenton, K. J., Therriault, H., Cantin, A. M., Fülöp, T., Payette, H., & Wagner, J. R. (2000) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.5.1194 · Cited by 67
The reductive capacity index of saliva obtained from donors of various ages
Kohen, R., Tirosh, O., & Kopolovich, K. (1992) · Experimental Gerontology · doi:10.1016/0531-5565(92)90040-7 · Cited by 50
Bauman, P. F., Smith, T. K., & Bray, T. Μ. (1988) · Journal of Nutrition · doi:10.1093/jn/118.8.1048 · Cited by 48
Solberg, H. E. (1986) · PubMed · Cited by 31
Depletion of circulating cyst(e)ine by oral and intravenous mesna
Stofer-Vogel, B., Cerny, T., Kupfer, A., Junker, E., & Lauterburg, B. H. (1993) · British Journal of Cancer · doi:10.1038/bjc.1993.391 · Cited by 30
The Role of the Cystathionine Pathway in Glutathione Regulation by Isolated Hepatocytes
Reed, D. J., & Beatty, P. W. (1978) · Proceedings in life sciences · doi:10.1007/978-3-642-67132-6_3 · Cited by 25
Petzki, K. J. (1980) · Food / Nahrung · doi:10.1002/food.19800240632 · Cited by 14
Darley-Usmar, V. M., & Starke-Reed, P. E. (2000) · Antioxidants and Redox Signaling · doi:10.1089/15230860050192143 · Cited by 11
Research works printed but not linked: 2
- Solberg, 1986, Statistical treatment of reference values in laboratory medicine, Scand. J. Clin. Lab. Invest. Suppl., 184, 125
- Chevion, 2000, Human studies related to protein oxidation, Free Radic. Res., 33, S99
Cited by
Sorted by citations
The importance of glutathione in human disease
Townsend, D. M., Tew, K. D., & Tapiero, H. (2003) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(03)00043-x · Cited by 2,009
Jones, D. P. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.1865 · Cited by 1,726
Self-citationRadical-free biology of oxidative stress
Jones, D. P. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00283.2008 · Cited by 1,213
Self-citationSULFUR AMINO ACID METABOLISM: Pathways for Production and Removal of Homocysteine and Cysteine
Stipanuk, M. H. (2004) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.24.012003.132418 · Cited by 997
Jones, D. P., & Sies, H. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6247 · Cited by 647
Self-citation
Metadata
- Authors
- Jones, D. P., Mody, V. C., Carlson, J. L., Lynn, M. J., & Sternberg, P.
- Affiliations
- Emory University (US)
- Corresponding author
- Jones, Dean P
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 33
- Issue
- 9
- Pages
- 1290-1300
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2067305246
- Cited by
- 392
- References
- 41
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 9 · 2023: 7 · 2022: 18 · 2021: 12 · 2020: 17 · 2019: 21 · 2018: 18 · 2017: 17 · 2016: 20 · 2015: 23 · 2014: 23 · 2013: 14 · 2012: 25
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (EY07892, EY0 6360, P30EY006360)
- National Institute of Environmental Health Sciences (ES09047, R01ES009047)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- oxidative stress, aging, antioxidant defense, age-related diseases
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Cysteine, Disulfides, Female, Glutathione, Humans, Kinetics, Male, Middle Aged, Models, Chemical, Oxidation-Reduction, Reference Values, Sulfhydryl Compounds, Age Distribution, Sex Distribution, Oxidative Stress, Glutathione Disulfide
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review