title: Inflamm-aging does not simply reflect increases in pro-inflammatory markers.
abstract: Many biodemographic studies use biomarkers of inflammation to understand or predict chronic disease and aging. Inflamm-aging, i.e. chronic low-grade inflammation during aging, is commonly characterized by pro-inflammatory biomarkers. However, most studies use just one marker at a time, sometimes leading to conflicting results due to complex interactions among the markers. A multidimensional approach allows a more robust interpretation of the various relationships between the markers. We applied principal component analysis (PCA) to 19 inflammatory biomarkers from the InCHIANTI study. We identified a clear, stable structure among the markers, with the first axis explaining inflammatory activation (both pro- and anti-inflammatory markers loaded strongly and positively) and the second axis innate immune response. The first but not the second axis was strongly correlated with age (r=0.56, p<0.0001, r=0.08 p=0.053), and both were strongly predictive of mortality (hazard ratios per PCA unit (95% CI): 1.33 (1.16-1.53) and 0.87 (0.76-0.98) respectively) and multiple chronic diseases, but in opposite directions. Both axes were more predictive than any individual markers for baseline chronic diseases and mortality. These results show that PCA can uncover a novel biological structure in the relationships among inflammatory markers, and that key axes of this structure play important roles in chronic disease.
authors.affiliation: Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12eAvenue North, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Morrisette-Thomas
authors.affiliation: Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12eAvenue North, Sherbrooke, QC J1H 5N4, Canada. Electronic address: Alan.Cohen@USherbrooke.ca.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Cohen
authors.affiliation: Research Center on Aging, Department of medecine, University of Sherbrooke, CSSS-IUGS, 1036 rue Belvédère Sud, Sherbrooke, QC J1H 4C4, Canada.
authors.forename: Tamàs
authors.initials: T
authors.lastname: Fülöp
authors.affiliation: Research Center on Aging, CSSS-IUGS, and Faculty of Physical education and sport, Department of Kinanthropology, University of Sherbrooke, Sherbrooke, Canada.
authors.forename: Éléonor
authors.initials: É
authors.lastname: Riesco
authors.affiliation: Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12eAvenue North, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Legault
authors.affiliation: Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12eAvenue North, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12eAvenue North, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Milot
authors.affiliation: Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12eAvenue North, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Françis
authors.initials: F
authors.lastname: Dusseault-Bélanger
authors.affiliation: Translational Gerontology Branch, Longitudinal Studies Section, National Institute on Aging, National Institutes of Health, MedStar Harbor Hospital, 3001 South Hanover Street, Baltimore, MD 21225, United States.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood*; D007558:Italy; D008297:Male; D008875:Middle Aged
chemical_list: D018836:Inflammation Mediators
keywords: Aging; Biomarker; Chronic disease; Inflammation; Multivariate