title: Cross-population validation of statistical distance as a measure of physiological dysregulation during aging.
abstract: Measuring physiological dysregulation during aging could be a key tool both to understand underlying aging mechanisms and to predict clinical outcomes in patients. However, most existing indices are either circular or hard to interpret biologically. Recently, we showed that statistical distance of 14 common blood biomarkers (a measure of how strange an individual's biomarker profile is) was associated with age and mortality in the WHAS II data set, validating its use as a measure of physiological dysregulation. Here, we extend the analyses to other data sets (WHAS I and InCHIANTI) to assess the stability of the measure across populations. We found that the statistical criteria used to determine the original 14 biomarkers produced diverging results across populations; in other words, had we started with a different data set, we would have chosen a different set of markers. Nonetheless, the same 14 markers (or the subset of 12 available for InCHIANTI) produced highly similar predictions of age and mortality. We include analyses of all combinatorial subsets of the markers and show that results do not depend much on biomarker choice or data set, but that more markers produce a stronger signal. We conclude that statistical distance as a measure of physiological dysregulation is stable across populations in Europe and North America.
authors.affiliation: Groupe de recherche PRIMUS, Dept. of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12(e) Ave N., Sherbrooke, QC J1H 5N4, Canada. Electronic address: Alan.Cohen@USherbrooke.ca.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Cohen
authors.affiliation: Groupe de recherche PRIMUS, Dept. of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12(e) Ave N., Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Milot
authors.affiliation: Groupe de recherche PRIMUS, Dept. of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12(e) Ave N., Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Groupe de recherche PRIMUS, Dept. of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12(e) Ave N., Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Legault
authors.affiliation: Mailman School of Public Health, Columbia University, 722 W. 168th Street, R1408, New York, NY 10032, USA.
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, MD 21225, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Aging; Biomarker; InCHIANTI; Mahalanobis distance; Physiological dysregulation; WHAS