title: Detection of a novel, integrative aging process suggests complex physiological integration.
abstract: Many studies of aging examine biomarkers one at a time, but complex systems theory and network theory suggest that interpretations of individual markers may be context-dependent. Here, we attempted to detect underlying processes governing the levels of many biomarkers simultaneously by applying principal components analysis to 43 common clinical biomarkers measured longitudinally in 3694 humans from three longitudinal cohort studies on two continents (Women's Health and Aging I & II, InCHIANTI, and the Baltimore Longitudinal Study on Aging). The first axis was associated with anemia, inflammation, and low levels of calcium and albumin. The axis structure was precisely reproduced in all three populations and in all demographic sub-populations (by sex, race, etc.); we call the process represented by the axis "integrated albunemia." Integrated albunemia increases and accelerates with age in all populations, and predicts mortality and frailty--but not chronic disease--even after controlling for age. This suggests a role in the aging process, though causality is not yet clear. Integrated albunemia behaves more stably across populations than its component biomarkers, and thus appears to represent a higher-order physiological process emerging from the structure of underlying regulatory networks. If this is correct, detection of this process has substantial implications for physiological organization more generally.
authors.affiliation: Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, 3001 12e Ave N, Sherbrooke, QC, J1H 5N4, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Cohen
authors.affiliation: Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières, 3351, boul. des Forges, C.P. 500, Trois-Rivières, QC, G9A 5H7, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Milot
authors.affiliation: Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, 3001 12e Ave N, 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, 3001 12e Ave N, Sherbrooke, QC, J1H 5N4, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bergeron
authors.affiliation: Department of Biology, University of Sherbrooke, 2500 boulevard de l'Université, Sherbrooke, QC, J1K 2R1, Canada.
authors.forename: Roxane
authors.initials: R
authors.lastname: Poirier
authors.affiliation: Department of Mathematics, University of Sherbrooke, 2500 boulevard de l'Université, Sherbrooke, QC, J1K 2R1, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Dusseault-Bélanger
authors.affiliation: Department of Geriatrics, University of Sherbrooke, 3001 12e Ave N, Sherbrooke, QC, J1H 5N4, Canada.
authors.forename: Tamàs
authors.initials: T
authors.lastname: Fülöp
authors.affiliation: Economics Department, ESG, Université du Québec à Montréal, 315 rue Sainte-Catherine Est, Montréal, QC, H2X 3X2, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Leroux
authors.affiliation: Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, 3001 12e Ave N, Sherbrooke, QC, J1H 5N4, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Legault
authors.affiliation: Translational Gerontology Branch, Longitudinal Studies Section, National Institute on Aging, National Institutes of Health, MedStar Harbor Hospital, 3001 S. Hanover Street, Baltimore, Maryland 21225, United States of America.
authors.forename: E Jeffrey
authors.initials: EJ
authors.lastname: Metter
authors.affiliation: Mailman School of Public Health, Columbia University, 722 W. 168th Street, R1408, New York, New York 10032, United States of America.
authors.forename: Linda P
authors.initials: LP
authors.lastname: Fried
authors.affiliation: Translational Gerontology Branch, Longitudinal Studies Section, National Institute on Aging, National Institutes of Health, MedStar Harbor Hospital, 3001 S. Hanover Street, Baltimore, Maryland 21225, United States of America.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000418:Albumins / Q000378:metabolism*; D000740:Anemia / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D055815:Young Adult
chemical_list: D000418:Albumins; D015415:Biomarkers; D002118:Calcium