Detection of a novel, integrative aging process suggests complex physiological integration

Alan A. Cohen, Emmanuel Milot, Qing Li, Patrick Bergeron, Roxane Poirier, Francis Dusseault-Bélanger, Tamàs Fülöp, Maxime Leroux, Véronique Legault, E. Jeffrey Metter, Linda P. Fried, Luigi Ferrucci

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere0116489
JournalPloS one
Issue number3
StatePublished - Mar 11 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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