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Mech Ageing Dev. 2013 Mar;134(3-4):110-7. doi: 10.1016/j.mad.2013.01.004. Epub 2013 Jan 31.

A novel statistical approach shows evidence for multi-system physiological dysregulation during aging.

Author information

1
Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, CHUS-Fleurimont, 3001 12e Avenue North, Sherbrooke, QC J1H 5N4, Canada. Alan.Cohen@USherbrooke.ca

Abstract

Previous studies have identified many biomarkers that are associated with aging and related outcomes, but the relevance of these markers for underlying processes and their relationship to hypothesized systemic dysregulation is not clear. We address this gap by presenting a novel method for measuring dysregulation via the joint distribution of multiple biomarkers and assessing associations of dysregulation with age and mortality. Using longitudinal data from the Women's Health and Aging Study, we selected a 14-marker subset from 63 blood measures: those that diverged from the baseline population mean with age. For the 14 markers and all combinatorial sub-subsets we calculated a multivariate distance called the Mahalanobis distance (MHBD) for all observations, indicating how "strange" each individual's biomarker profile was relative to the baseline population mean. In most models, MHBD correlated positively with age, MHBD increased within individuals over time, and higher MHBD predicted higher risk of subsequent mortality. Predictive power increased as more variables were incorporated into the calculation of MHBD. Biomarkers from multiple systems were implicated. These results support hypotheses of simultaneous dysregulation in multiple systems and confirm the need for longitudinal, multivariate approaches to understanding biomarkers in aging.

PMID:
23376244
PMCID:
PMC3971434
DOI:
10.1016/j.mad.2013.01.004
[Indexed for MEDLINE]
Free PMC Article
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