Association of Markers of Inflammation, the Kynurenine Pathway and B Vitamins with Age and Mortality, and a Signature of Inflammaging.
J Gerontol A Biol Sci Med Sci
; 77(4): 826-836, 2022 04 01.
Article
em En
| MEDLINE
| ID: mdl-34117761
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 HKXA (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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complexo Vitamínico B
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Aged
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article