876Association of blood markers of inflammation, vitamin status and the kynurenine pathway with age and all-cause mortality

Abstract

\n \n \n Inflammation is a key feature of aging and a cause of numerous diseases. We investigated the association of 35 blood markers involved in inflammatory processes with age and mortality and developed a signature of ‘inflammaging’.\n \n \n \n Thirty-five blood markers relating to the kynurenine pathway, vitamin status, and inflammation were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (1990-1994, median age 59 years) and follow-up (2003-2007, median age 70 years). Associations of each marker with age and all-cause mortality were assessed using linear and Cox regression, respectively. A signature of inflammaging was obtained via Lasso regression of age on the markers and tested for association with mortality; we compared mortality associations for this signature and two weighted scores across all markers associated with age and mortality, respectively.\n \n \n \n Most markers (29/35) were associated with age, with strongest associations observed for cystatin C, neopterin, quinolinic acid, and the kynurenine/tryptophan ratio, PAr index, and 3-hydroxykynurenine/xanthurenic acid ratio. Many markers (14/35) showed strong associations with mortality in particular neopterin, quinolinic acid, HK/XA, PAr index, CRP, IL-6 and KTr. The inflammaging signature included six markers and showed strong association with mortality (HR\u2009=\u20091.5, 95%CI: 1.3-1.7), almost as strong as the association of weighted scores combining all measured markers.\n \n \n \n Our study highlights the key role played by markers of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers.\n \n \n \n A signature of ‘inflammaging’ based on 6 markers may be useful to better predict mortality.\n