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

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: .
Mechanisms of ageing and development (Impact Factor: 3.51). 01/2013; 134(3). DOI: 10.1016/j.mad.2013.01.004
Source: PubMed

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)(1) 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.

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Available from: Emmanuel Milot, Aug 27, 2015
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    • "Many of our analyses have been replicated across a very large number of biomarker combinations. Our initial analyses used a group of 14 markers identified through a statistical selection procedure, and were replicated on every combination of these 14, i.e. 16 383 combinations (Cohen et al. 2013), (2014). We then used the full set of 44, testing 5000 random combinations for each possible number between 1 and 44, or all combinations when less than 5000 existed (Cohen et al. 2015a). "
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