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dc.contributor.authorDugué, Pierre-Antoine
dc.contributor.authorHodge, Allison M.
dc.contributor.authorUlvik, Arve
dc.contributor.authorUeland, Per Magne
dc.contributor.authorMidttun, Øyvind
dc.contributor.authorRinaldi, Sabina
dc.contributor.authorMacInnis, Robert J.
dc.contributor.authorLi, Sherly X.
dc.contributor.authorMeyer, Klaus
dc.contributor.authorNavionis, Anne-Sophie
dc.contributor.authorFlicker, Leon
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorEnglish, Dallas R.
dc.contributor.authorVineis, Paolo
dc.contributor.authorTell, Grethe S.
dc.contributor.authorSouthey, Melissa C.
dc.contributor.authorMilne, Roger L.
dc.contributor.authorGiles, Graham G.
dc.date.accessioned2022-03-25T14:13:21Z
dc.date.available2022-03-25T14:13:21Z
dc.date.created2022-01-26T08:58:26Z
dc.date.issued2021
dc.identifier.issn1079-5006
dc.identifier.urihttps://hdl.handle.net/11250/2987713
dc.descriptionUnder embargo until: 2022-06-12en_US
dc.description.abstractBackground Inflammation is a key feature of aging. We aimed to (i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality and (ii) develop a signature of “inflammaging.” Methods Thirty-four blood markers relating to inflammation, B vitamin status, and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age = 59 years) and follow-up (median age = 70 years). Associations with age and mortality were assessed using linear and Cox regression, respectively. A parsimonious signature of inflammaging was developed and its association with mortality was compared with 2 marker scores calculated across all markers associated with age and mortality, respectively. Results The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), several markers of the kynurenine pathway and derived indices KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5′-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, C-reactive protein, quinolinic acid, PAr index, and KTR. The inflammaging signature included 10 markers and was strongly associated with mortality (hazard ratio [HR] per SD = 1.40, 95% CI: 1.24–1.57, p = 2 × 10−8), similar to scores based on all age-associated (HR = 1.38, 95% CI: 1.23–1.55, p = 4 × 10−8) and mortality-associated markers (HR = 1.43, 95% CI: 1.28–1.60, p = 1 × 10−10), respectively. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study. Conclusion Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on 10 markers was strongly associated with mortality.en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.titleAssociation of Markers of Inflammation, the Kynurenine Pathway and B Vitamins with Age and Mortality, and a Signature of Inflammagingen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionacceptedVersionen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode2
dc.identifier.doihttps://doi.org/10.1093/gerona/glab163
dc.identifier.cristin1990060
dc.source.journalThe journals of gerontology. Series A, Biological sciences and medical sciencesen_US
dc.identifier.citationThe journals of gerontology. Series A, Biological sciences and medical sciences. 2021en_US


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