TY - JOUR
T1 - Detection of a novel, integrative aging process suggests complex physiological integration
AU - Cohen, Alan A.
AU - Milot, Emmanuel
AU - Li, Qing
AU - Bergeron, Patrick
AU - Poirier, Roxane
AU - Dusseault-Bélanger, Francis
AU - Fülöp, Tamàs
AU - Leroux, Maxime
AU - Legault, Véronique
AU - Metter, E. Jeffrey
AU - Fried, Linda P.
AU - Ferrucci, Luigi
N1 - Funding Information:
BH Singer and DEL Promislow provided comments on the manuscript. AAC is a member of the FRQ-S-supported Centre de recherche sur le vieillissement and Centre de recherche du CHUS, and is a funded Research Scholar of the FRQ-S. This research was supported by CIHR grant #s 110789, 120305, 119485 and by NSERC Discovery Grant # 402079-2011, as well as by the Intramural Research Program of the National Institute on Aging.
PY - 2015/3/11
Y1 - 2015/3/11
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0116489
DO - 10.1371/journal.pone.0116489
M3 - Article
C2 - 25761112
AN - SCOPUS:84924347534
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 3
M1 - e0116489
ER -