CoChat
Sign Up
Cited by 46Antioxidant Activity and Oxidative StressGenetics, Aging, and Longevity in Model OrganismsRedox biology and oxidative stress

Associations between Specific Redox Biomarkers and Age in a Large European Cohort: The MARK‐AGE Project

Open access
Weber, Daniela, Stuetz, Wolfgang, Toussaint, Olivier, Debacq-Chainiaux, Florence, Dollé, Martijn E. T., Jansen, Eugène, Gonos, Efstathios S., Franceschi, Claudio +7 more·2017·Oxidative Medicine and Cellular Longevity
DOI 10.1155/2017/1401452PMC PMC5539926
Open this paper in CoChat — free accountOpen PDF

Abstract

Oxidative stress and antioxidants play a role in age‐related diseases and in the aging process. We here present data on protein carbonyls, 3‐nitrotyrosine, malondialdehyde, and cellular and plasma antioxidants (glutathione, cysteine, ascorbic acid, uric acid, α‐tocopherol, and lycopene) and their relation with age in the European multicenter study MARK‐AGE. To avoid confounding, only data from countries which recruited subjects from all three study groups (five of eight centers) and only participants aged ≥55 years were selected resulting in data from 1559 participants. These included subjects from (1) the general population, (2) members from long‐living families, and (3) their spouses. In addition, 683 middle‐aged reference participants (35–54 years) served as a control. After adjustment for age, BMI, smoking status, gender, and country, there were differences in protein carbonyls, malondialdehyde, 3‐nitrotyrosine, α‐tocopherol, cysteine, and glutathione between the 3 study groups. Protein carbonyls and 3‐nitrotyrosine as well as cysteine, uric acid, and lycopene were identified as independent biomarkers with the highest correlation with age. Interestingly, from all antioxidants measured, only lycopene was lower in all aged groups and from the oxidative stress biomarkers, only 3‐nitrotyrosine was increased in the descendants from long‐living families compared to the middle‐aged control group. We conclude that both lifestyle and genetics may be important contributors to redox biomarkers in an aging population.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1155/2017/1401452

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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 two of three MARK-AGE cohorts, no differences in 3-NT were found between age groups.

    “Two of three cohorts showed no differences between the age groups,”

    From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [194]

    The Discussion (page unavailable) says there might have been no dramatic difference in 3-nitrotyrosine across age groups, and the Results (page unavailable) report that only GO had higher 3-nitrotyrosine than the middle-aged reference group. Neither passage establishes the claimed finding specifically for age-group comparisons within two of the three MARK-AGE cohorts. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • In the RASIG group of the MARK-AGE study, there is a positive correlation between 3-NT levels and age (plasma, ELISA).

    “Positive correlation between 3-NT levels and age in RASIG group”

    From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [194]

    The Results report a positive correlation between 3-nitrotyrosine and age, and Methods §2.5 identifies plasma ELISA as the measurement method. The Results do not specify that this age correlation was found within the RASIG group; the statement about similar RASIG correlations refers to correlations among biomarkers, not with age. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Weber et al. found no correlation between protein carbonyls and aging in two of three cohorts from the European MARK-AGE study.

    “Weber et al. found no correlation between protein carbonyls and aging in two of three cohorts from the European MARK-AGE study”

    From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [194]

  • In the MARK-AGE project groups (RASIG n = 794, GO n = 493, SGO n = 272), plasma MDA levels show no correlation with age across the four age groups (55-59, 60-64, 65-69, and 70-75 years), as measured by RP-HPLC.

    “| Aging | Plasma | 3 study groups from MARK-AGE project:RASIG (n = 794), GO (n = 493), SGO(n = 272)Participants divided in 4 groups:55-59, 60–64, 65–69 and 70–75 years | RP-HPLC | No correlation in all groups between MDA levels and age | [194] |”

    From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [194]

  • In the MARK-AGE study, two of three cohorts showed no differences in 3-NT levels between age groups.

    “Two of three cohorts showed no differences between the age groups”

    From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [194]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 51 · Cited by 46

Research works printed but not linked: 46

  1. [1]Atkuri K. R. Mantovani J. J. Herzenberg L. A. Herzenberg L. A. N-Acetylcysteine—a safe antidote for cysteine/glutathione deficiency Current Opinion in Pharmacology 2007 7 355 359 10.1016/j.coph.2007.04.005 2-s2.0-34548072307 34548072307 17602868 PMC4540061 · DOI · Paper page
  2. [2]Greilberger J. Koidl C. Greilberger M. Malondialdehyde, carbonyl proteins and albumin-disulphide as useful oxidative markers in mild cognitive impairment and Alzheimer’s disease Free Radical Research 2008 42 633 638 18654878
  3. [4]Mutlu-Turkoglu U. Ilhan E. Oztezcan S. Kuru A. Aykac-Toker G. Uysal M. Age-related increases in plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in elderly subjects Clinical Biochemistry 2003 36 397 400 10.1016/S0009-9120(03)00035-3 2-s2.0-0038204747 0038204747 12849873 · DOI · Paper page
  4. [5]Mehdi M. M. Rizvi S. I. Plasma protein hydroperoxides during aging in humans: correlation with paraoxonase 1 (PON1) arylesterase activity and plasma total thiols Archives of Medical Research 2013 44 136 141 10.1016/j.arcmed.2013.01.003 2-s2.0-84875254238 84875254238 23376056 · DOI
  5. [6]Pandey K. B. Mehdi M. M. Maurya P. K. Rizvi S. I. Plasma protein oxidation and its correlation with antioxidant potential during human aging Disease Markers 2010 29 31 36 10.3233/DMA-2010-0723 2-s2.0-77957224133 77957224133 20826915 PMC3835284 · DOI
  6. [7]Schottker B. Brenner H. Jansen E. H. Evidence for the free radical/oxidative stress theory of ageing from the CHANCES consortium: a meta-analysis of individual participant data BMC Medicine 2015 13 p. 300 PMC4678534 26666526
  7. [8]Saum K. U. Dieffenbach A. K. Jansen E. H. Association between oxidative stress and frailty in an elderly German population: results from the ESTHER cohort study Gerontology 2015 61 407 415 10.1159/000380881 2-s2.0-84942091966 84942091966 25924722 · DOI
  8. [9]Schottker B. Saum K. U. Jansen E. H. Oxidative stress markers and all-cause mortality at older age: a population-based cohort study The Journals of Gerontology Series A, Biological Sciences and Medical Sciences 2015 70 518 524 10.1093/gerona/glu111 2-s2.0-84926674717 84926674717 25070660 · DOI
  9. [10]Semba R. D. Ferrucci L. Sun K. Oxidative stress is associated with greater mortality in older women living in the community Journal of the American Geriatrics Society 2007 55 1421 1425 10.1111/j.1532-5415.2007.01308.x 2-s2.0-34548248088 34548248088 17767685 PMC2645668 · DOI
  10. [11]Breusing N. Grune T. Biomarkers of protein oxidation from a chemical, biological and medical point of view Experimental Gerontology 2010 45 733 737 10.1016/j.exger.2010.04.004 2-s2.0-77957008533 77957008533 20403419 · DOI
  11. [12]Burkle A. Moreno-Villanueva M. Bernhard J. MARK-AGE biomarkers of ageing Mechanisms of Ageing and Development 2015 151 2 12 10.1016/j.mad.2015.03.006 2-s2.0-84941698753 84941698753 25818235 · DOI
  12. [13]Capri M. Moreno-Villanueva M. Cevenini E. MARK-AGE population: from the human model to new insights Mechanisms of Ageing and Development 2015 151 13 17 10.1016/j.mad.2015.03.010 2-s2.0-84947025419 84947025419 25843237 · DOI
  13. [14]Moreno-Villanueva M. Capri M. Breusing N. MARK-AGE standard operating procedures (SOPs): a successful effort Mechanisms of Ageing and Development 2015 151 18 25 10.1016/j.mad.2015.03.007 2-s2.0-84947045497 84947045497 25817206 · DOI
  14. [15]Moreno-Villanueva M. Kotter T. Sindlinger T. The MARK-AGE phenotypic database: structure and strategy Mechanisms of Ageing and Development 2015 151 26 30 10.1016/j.mad.2015.03.005 2-s2.0-84947030767 84947030767 25817205 · DOI
  15. [16]Franceschi C. Bezrukov V. Blanche H. Genetics of healthy aging in Europe: the EU-integrated project GEHA (Genetics of healthy aging) Annals of the New York Academy of Sciences 2007 1100 21 45 10.1196/annals.1395.003 2-s2.0-34249744331 34249744331 17460163 · DOI
  16. [17]Chen W. Zhao Y. Seefeldt T. Guan X. Determination of thiols and disulfides via HPLC quantification of 5-thio-2-nitrobenzoic acid Journal of Pharmaceutical and Biomedical Analysis 2008 48 5 1375 1380 10.1016/j.jpba.2008.08.033 2-s2.0-58149492821 18926658 PMC2684446 · DOI
  17. [18]Hongsibsong S. Stuetz W. Sus N. Prapamontol T. Grune T. Frank J. Dietary exposure to continuous small doses of α-cypermethrin in the presence or absence of dietary curcumin does not induce oxidative stress in male Wistar rats Toxicology Reports 2014 1 1106 1114 10.1016/j.toxrep.2014.10.025 2-s2.0-84922728965 PMC5598094 28962322 · DOI
  18. [19]Wong S. H. Knight J. A. Hopfer S. M. Zaharia O. Leach C. N. Jr. Sunderman F. W. Jr. Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct Clinical Chemistry 1987 33 214 220 3802504
  19. [20]Weber D. Stuetz W. Bernhard W. Oxidative stress markers and micronutrients in maternal and cord blood in relation to neonatal outcome European Journal of Clinical Nutrition 2014 68 215 222 24327121
  20. [21]Buss H. Chan T. P. Sluis K. B. Domigan N. M. Winterbourn C. C. Protein carbonyl measurement by a sensitive ELISA method Free Radical Biology and Medicine 1997 23 361 366 10.1016/S0891-5849(97)00104-4 2-s2.0-0030910932 9214571 · DOI
  21. [22]Stuetz W. Weber D. Dolle M. E. Plasma carotenoids, tocopherols, and retinol in the age-stratified (35–74 years) general population: a cross-sectional study in six European countries Nutrients 2016 8 10 p. 64 27706032 PMC5084002
  22. [23]Dalle-Donne I. Rossi R. Giustarini D. Milzani A. Colombo R. Protein carbonyl groups as biomarkers of oxidative stress Clinica Chimica Acta 2003 329 23 38 10.1016/S0009-8981(03)00003-2 2-s2.0-0037363715 12589963 · DOI
  23. [24]Levine R. L. Garland D. Oliver C. N. Determination of carbonyl content in oxidatively modified proteins Methods in Enzymology 1990 186 464 478 1978225
  24. [25]Komosinska-Vassev K. Olczyk P. Winsz-Szczotka K. Klimek K. Olczyk K. Plasma biomarkers of oxidative and AGE-mediated damage of proteins and glycosaminoglycans during healthy ageing: a possible association with ECM metabolism Mechanisms of Ageing and Development 2012 133 538 548 10.1016/j.mad.2012.07.001 2-s2.0-84865352202 84865352202 22813851 · DOI
  25. [26]Cakatay U. Kayali R. Uzun H. Relation of plasma protein oxidation parameters and paraoxonase activity in the ageing population Clinical and Experimental Medicine 2008 8 51 57 10.1007/s10238-008-0156-0 2-s2.0-43449131541 43449131541 18385941 · DOI
  26. [27]Herce-Pagliai C. Kotecha S. Shuker D. E. Analytical methods for 3-nitrotyrosine as a marker of exposure to reactive nitrogen species: a review Nitric Oxide: Biology and Chemistry 1998 2 324 336 10.1006/niox.1998.0192 2-s2.0-0032456059 10100488 · DOI
  27. [28]Van Der Vliet A. Eiserich J. P. Halliwell B. Cross C. E. Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite. A potential additional mechanism of nitric oxide-dependent toxicity Journal of Biological Chemistry 1997 272 7617 7625 9065416
  28. [29]Frijhoff J. Winyard P. G. Zarkovic N. Clinical relevance of biomarkers of oxidative stress Antioxidants & Redox Signaling 2015 23 1144 1170 10.1089/ars.2015.6317 2-s2.0-84947743712 26415143 PMC4657513 · DOI
  29. [30]von Haehling S. Bode-Boger S. M. Martens-Lobenhoffer J. Elevated levels of asymmetric dimethylarginine in chronic heart failure: a pathophysiologic link between oxygen radical load and impaired vasodilator capacity and the therapeutic effect of allopurinol Clinical Pharmacology and Therapeutics 2010 88 506 512 10.1038/clpt.2010.116 2-s2.0-77957021340 77957021340 20827268 · DOI
  30. [32]Yamakura F. Taka H. Fujimura T. Murayama K. Inactivation of human manganese-superoxide dismutase by peroxynitrite is caused by exclusive nitration of tyrosine 34 to 3-nitrotyrosine The Journal of Biological Chemistry 1998 273 14085 14089 10.1074/jbc.273.23.14085 2-s2.0-0032486405 0032486405 9603906 · DOI
  31. [33]Vadseth C. Souza J. M. Thomson L. Pro-thrombotic state induced by post-translational modification of fibrinogen by reactive nitrogen species The Journal of Biological Chemistry 2004 279 8820 8826 10.1074/jbc.M306101200 2-s2.0-10744226883 10744226883 14681238 · DOI
  32. [34]Block G. Dietrich M. Norkus E. Intraindividual variability of plasma antioxidants, markers of oxidative stress, C-reactive protein, cotinine, and other biomarkers Epidemiology 2006 17 404 412 10.1097/01.ede.0000220655.53323.e9 2-s2.0-33748108803 33748108803 16755268 · DOI
  33. [35]Block G. Dietrich M. Norkus E. P. Factors associated with oxidative stress in human populations American Journal of Epidemiology 2002 156 274 285 10.1093/aje/kwf029 2-s2.0-0036682194 0036682194 12142263 · DOI
  34. [36]Samiec P. S. Drews-Botsch C. Flagg E. W. Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes Free Radical Biology and Medicine 1998 24 699 704 10.1016/S0891-5849(97)00286-4 2-s2.0-0032521155 9586798 · DOI
  35. [37]Sekhar R. V. Patel S. G. Guthikonda A. P. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation The American Journal of Clinical Nutrition 2011 94 847 853 10.3945/ajcn.110.003483 2-s2.0-80051974890 80051974890 21795440 PMC3155927 · DOI · Paper page
  36. [38]Giustarini D. Dalle-Donne I. Lorenzini S. Milzani A. Rossi R. Age-related influence on thiol, disulfide, and protein-mixed disulfide levels in human plasma The Journals of Gerontology Series A, Biological Sciences and Medical Sciences 2006 61 1030 1038 10.1093/gerona/61.10.1030 33750906064 17077195 · DOI
  37. [40]Jones D. P. Carlson J. L. Mody V. C. Cai J. Lynn M. J. Sternberg P. Redox state of glutathione in human plasma Free Radical Biology & Medicine 2000 28 625 635 10.1016/S0891-5849(99)00275-0 2-s2.0-0034652725 10719244 · DOI
  38. [41]Moriarty-Craige S. E. Jones D. P. Extracellular thiols and thiol/disulfide redox in metabolism Annual Review of Nutrition 2004 24 481 509 10.1146/annurev.nutr.24.012003.132208 2-s2.0-3142685079 3142685079 15189129 · DOI
  39. [42]Droge W. Oxidative stress and ageing: is ageing a cysteine deficiency syndrome? Philosophical Transactions of the Royal Society of London Series B, Biological Sciences 2005 360 2355 2372 10.1098/rstb.2005.1770 2-s2.0-33745247801 33745247801 16321806 PMC1569588 · DOI
  40. [43]Yin J. Ren W. Yang G. L-cysteine metabolism and its nutritional implications Molecular Nutrition & Food Research 2016 60 134 146 10.1002/mnfr.201500031 2-s2.0-84952935434 25929483 · DOI
  41. [44]Lippi G. Montagnana M. Franchini M. Favaloro E. J. Targher G. The paradoxical relationship between serum uric acid and cardiovascular disease Clinica Chimica Acta 2008 392 1 7 10.1016/j.cca.2008.02.024 2-s2.0-42749087690 18348869 · DOI
  42. [45]Block G. Norkus E. Hudes M. Mandel S. Helzlsouer K. Which plasma antioxidants are most related to fruit and vegetable consumption? American Journal of Epidemiology 2001 154 1113 1118 10.1093/aje/154.12.1113 2-s2.0-0035892865 0035892865 11744516 · DOI
  43. [47]Sies H. Stahl W. Vitamins E and C, beta-carotene, and other carotenoids as antioxidants The American Journal of Clinical Nutrition 1995 62 1315S 1321S 7495226
  44. [48]Weber D. Kneschke N. Grimm S. Bergheim I. Breusing N. Grune T. Rapid and sensitive determination of protein-nitrotyrosine by ELISA: application to human plasma Free Radical Research 2012 46 276 285 10.3109/10715762.2011.652627 2-s2.0-84857333927 84857333927 22276750 · DOI · Paper page
  45. [49]Augustyniak E. Adam A. Wojdyla K. Validation of protein carbonyl measurement: a multi-centre study Redox Biology 2015 4 149 157 10.1016/j.redox.2014.12.014 2-s2.0-84920386346 84920386346 25560243 PMC4309846 · DOI · Paper page
  46. [50]Giustarini D. Dalle-Donne I. Tsikas D. Rossi R. Oxidative stress and human diseases: origin, link, measurement, mechanisms, and biomarkers Critical Reviews in Clinical Laboratory Sciences 2009 46 241 281 10.3109/10408360903142326 2-s2.0-71849114694 71849114694 19958214 · DOI

Authors
Weber, D., Stuetz, W., Toussaint, O., Debacq-Chainiaux, F., Dollé, M. E. T., Jansen, E., Gonos, E. S., Franceschi, C., Sikora, E., Hervonen, A., Breusing, N., Sindlinger, T., Moreno-Villanueva, M., Bürkle, A., & Grune, T.
Affiliations
  • German Institute of Human Nutrition (DE)
  • University of Hohenheim (DE)
  • University of Namur (BE)
  • National Institute for Public Health and the Environment (NL)
  • National Hellenic Research Foundation (GR)
  • University of Bologna (IT)
  • Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
  • University of Tampere (FI)
  • University of Konstanz (DE)
  • German Centre for Cardiovascular Research (DE)
Corresponding author
Weber, Daniela
ORCID
Venue
Oxidative Medicine and Cellular Longevity
Publisher
Wiley
Published
2017-01
Volume
2017
Issue
1
Pages
1401452-1401452
ISSN
  • 1942-0994 (ISSN-L)
  • 1942-0900
DOI
10.1155/2017/1401452
PMC
PMC5539926
OpenAlex
W2736518260
Cited by
46
References
51
Citations by year
2026: 2 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 1
FWCI
3.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository of the University of Namur (publishedVersion, cc-by)
  • Tampere University Institutional Repository (Tampere University) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • National Hellenic Research Foundation Helios Repository (National Hellenic Research Foundation) (submittedVersion)
  • KOPS (University of Konstanz) (submittedVersion, cc-by)
  • Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
  • Rivm (National Institute for Public Health and the Environment) (submittedVersion)
  • Tampere University Institutional Repository (Tampere University) (submittedVersion, cc-by)
Funders
Seventh Framework Programme (200880)
Topics
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • 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
Keywords
redox biomarkers, aging, oxidative stress, antioxidants, protein carbonyls, nitrotyrosine, malondialdehyde, glutathione, cysteine, uric acid, lycopene, alpha-tocopherol, vitamin C, age-related diseases
MeSH terms
Lycopene, Adult, Antioxidants, Ascorbic Acid, Carotenoids, Female, Glutathione, Humans, Male, Malondialdehyde, Middle Aged, Oxidation-Reduction, Tyrosine, Uric Acid, Lipid Peroxidation, Biomarkers, Oxidative Stress, alpha-Tocopherol

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