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Detection of a Novel, Integrative Aging Process Suggests Complex Physiological Integration

Author

Listed:
  • 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

Abstract

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.

Suggested Citation

  • 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 Fe, 2015. "Detection of a Novel, Integrative Aging Process Suggests Complex Physiological Integration," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-26, March.
    • Handle: RePEc:plo:pone00:0116489
    DOI: 10.1371/journal.pone.0116489
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    References listed on IDEAS

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    2. Hadfield, Jarrod D., 2010. "MCMC Methods for Multi-Response Generalized Linear Mixed Models: The MCMCglmm R Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 33(i02).
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    4. Leonard Guarente & Cynthia Kenyon, 2000. "Genetic pathways that regulate ageing in model organisms," Nature, Nature, vol. 408(6809), pages 255-262, November.
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