1. Association of Markers of Inflammation, the Kynurenine Pathway and B Vitamins with Age and Mortality, and a Signature of Inflammaging.
- Author
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Dugué, Pierre-Antoine, Hodge, Allison M, Ulvik, Arve, Ueland, Per M, Midttun, Øivind, Rinaldi, Sabina, MacInnis, Robert J, Li, Sherly X, Meyer, Klaus, Navionis, Anne-Sophie, Flicker, Leon, Severi, Gianluca, English, Dallas R, Vineis, Paolo, Tell, Grethe S, Southey, Melissa C, Milne, Roger L, and Giles, Graham G
- Subjects
VITAMIN B complex ,KYNURENINE ,TUMOR necrosis factors ,QUINOLINIC acid ,VITAMIN B6 ,AMINO acid metabolism ,INFLAMMATION ,RESEARCH funding ,LONGITUDINAL method - Abstract
Background: 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. [ABSTRACT FROM AUTHOR]- Published
- 2022
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